Talk:Immune System Development

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Cite this page: Hill, M.A. (2024, June 23) Embryology Immune System Development. Retrieved from

Note much of the current immune research refers to the postnatal or adult system.

Maternal Immune


Choi JH, Zhong X, Zhang Z, Su L, McAlpine W, Misawa T, Liao TC, Zhan X, Russell J, Ludwig S, Li X, Tang M, Anderton P, Moresco EMY & Beutler B. (2020). Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development. J. Exp. Med. , 217, . PMID: 31985756 DOI.

Essential cell-extrinsic requirement for PDIA6 in lymphoid and myeloid development

Abstract In a forward genetic screen of N-ethyl-N-nitrosourea (ENU)-induced mutant mice for aberrant immune function, we identified mice with a syndromic disorder marked by growth retardation, diabetes, premature death, and severe lymphoid and myeloid hypoplasia together with diminished T cell-independent (TI) antibody responses. The causative mutation was in Pdia6, an essential gene encoding protein disulfide isomerase A6 (PDIA6), an oxidoreductase that functions in nascent protein folding in the endoplasmic reticulum. The immune deficiency caused by the Pdia6 mutation was, with the exception of a residual T cell developmental defect, completely rescued in irradiated wild-type recipients of PDIA6-deficient bone marrow cells, both in the absence or presence of competition. The viable hypomorphic allele uncovered in these studies reveals an essential role for PDIA6 in hematopoiesis, but one extrinsic to cells of the hematopoietic lineage. We show evidence that this role is in the proper folding of Wnt3a, BAFF, IL-7, and perhaps other factors produced by the extra-hematopoietic compartment that contribute to the development and lineage commitment of hematopoietic cells. © 2020 Choi et al. PMID: 31985756 DOI: 10.1084/jem.20190006


Insights into immune system development and function from mouse T-cell repertoires

Proc Natl Acad Sci U S A. 2017 Feb 14. pii: 201700241. doi: 10.1073/pnas.1700241114.

Sethna Z1, Elhanati Y1,2, Dudgeon CS3, Callan CG Jr4, Levine AJ5, Mora T6, Walczak AM2.


The ability of the adaptive immune system to respond to arbitrary pathogens stems from the broad diversity of immune cell surface receptors. This diversity originates in a stochastic DNA editing process (VDJ recombination) that acts on the surface receptor gene each time a new immune cell is created from a stem cell. By analyzing T-cell receptor (TCR) sequence repertoires taken from the blood and thymus of mice of different ages, we quantify the changes in the VDJ recombination process that occur from embryo to young adult. We find a rapid increase with age in the number of random insertions and a dramatic increase in diversity. Because the blood accumulates thymic output over time, blood repertoires are mixtures of different statistical recombination processes, and we unravel the mixture statistics to obtain a picture of the time evolution of the early immune system. Sequence repertoire analysis also allows us to detect the statistical impact of selection on the output of the VDJ recombination process. The effects we find are nearly identical between thymus and blood, suggesting that our analysis mainly detects selection for proper folding of the TCR receptor protein. We further find that selection is weaker in laboratory mice than in humans and it does not affect the diversity of the repertoire. KEYWORDS: T cells; VDJ recombination; immunology; mouse; sequencing

PMID 28196891 DOI: 10.1073/pnas.1700241114


Tie1 is required for lymphatic valve and collecting vessel development

Dev Biol. 2015 Jan 7. pii: S0012-1606(14)00651-4. doi: 10.1016/j.ydbio.2014.12.021. [Epub ahead of print]

Qu X1, Zhou B2, Scott Baldwin H3.


Tie1 is a receptor tyrosine kinase with broad expression in embryonic endothelium. Reduction of Tie1 levels in mouse embryos with a hypomorphic Tie1 allele resulted in abnormal lymphatic patterning and architecture, decreased lymphatic draining efficiency, and ultimately, embryonic demise. Here we report that Tie1 is present uniformly throughout the lymphatics and from late embryonic/early postnatal stages, becomes more restricted to lymphatic valve regions. To investigate later events of lymphatic development, we employed Cre-loxP recombination utilizing a floxed Tie1 allele and an Nfatc1Cre line, to provide loxP excision predominantly in lymphatic endothelium and developing valves. Interestingly, unlike the early prenatal defects previously described by ubiquitous endothelial deletion, excision of Tie1 with Nfatc1Cre resulted in abnormal lymphatic defects in postnatal mice and was characterized by agenesis of lymphatic valves and a deficiency of collecting lymphatic vessels. Attenuation of Tie1 signaling in lymphatic endothelium prevented initiation of lymphatic valve specification by Prox1 high expression lymphatic endothelial cells that is associated with the onset of turbulent flow in the lymphatic circulation. Our findings reveal a fundamental role for Tie signaling during lymphatic vessel remodeling and valve morphogenesis and implicate it as a candidate gene involved in primary lymphedema. Copyright © 2015. Published by Elsevier Inc. KEYWORDS: Lymphatic valve; Lymphatic vessel remodeling; Lymphovenous valve; Prox1; Tie1; conditional knockout

PMID 25576926


A review of the innate immune defence of the human foetus and newborn, with the emphasis on antimicrobial peptides

Acta Paediatr. 2014 Oct;103(10):1000-8. doi: 10.1111/apa.12700. Epub 2014 Jun 23.

Kai-Larsen Y1, Gudmundsson GH, Agerberth B. Author information Abstract At birth, the foetus makes the transition from the uterus to a world full of microbes. The newborn baby needs protection against potential invading pathogens and needs to establish a normal microbiota. CONCLUSION: Antimicrobial peptides and proteins are key effector molecules of innate immunity and are also important immunomodulators. Their presence in the cells and tissues of the uterus, foetus and the neonate indicates an important role in immunity during pregnancy and in early life. ©2014 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd. KEYWORDS: Antimicrobial proteins; Defensins; Host defence; LL-37; Neonate PMID: 24861898 DOI: 10.1111/apa.12700

Lymphatic system: An active pathway for immune protection

Semin Cell Dev Biol. 2014 Dec 19. pii: S1084-9521(14)00322-X. doi: 10.1016/j.semcdb.2014.11.012. [Epub ahead of print]

Liao S1, von der Weid PY2.


Lymphatic vessels are well known to participate in the immune response by providing the structural and functional support for the delivery of antigens and antigen presenting cells to draining lymph nodes. Recent advances have improved our understanding of how the lymphatic system works and how it participates to the development of immune responses. New findings suggest that the lymphatic system may control the ultimate immune response through a number of ways which may include guiding antigen/dendritic cells (DC) entry into initial lymphatics at the periphery; promoting antigen/DC trafficking through afferent lymphatic vessels by actively facilitating lymph and cell movement; enabling antigen presentation in lymph nodes via a network of lymphatic endothelial cells and lymph node stroma cell and finally by direct lymphocytes exit from lymph nodes. The same mechanisms are likely also important to maintain peripheral tolerance. In this review we will discuss how the morphology and gene expression profile of the lymphatic endothelial cells in lymphatic vessels and lymph nodes provides a highly efficient pathway to initiate immune responses. The fundamental understanding of how lymphatic system participates in immune regulation will guide the research on lymphatic function in various diseases. Copyright © 2014 Elsevier Ltd. All rights reserved. KEYWORDS: Antigen delivery; Dendritic cell trafficking; Immune regulation; Lymph node; Lymphatic function\

PMID 25534659

Comparative and developmental anatomy of cardiac lymphatics

ScientificWorldJournal. 2014 Jan 27;2014:183170. doi: 10.1155/2014/183170. eCollection 2014.

Ratajska A1, Gula G2, Flaht-Zabost A1, Czarnowska E3, Ciszek B4, Jankowska-Steifer E5, Niderla-Bielinska J5, Radomska-Lesniewska D5. Author information


The role of the cardiac lymphatic system has been recently appreciated since lymphatic disturbances take part in various heart pathologies. This review presents the current knowledge about normal anatomy and structure of lymphatics and their prenatal development for a better understanding of the proper functioning of this system in relation to coronary circulation. Lymphatics of the heart consist of terminal capillaries of various diameters, capillary plexuses that drain continuously subendocardial, myocardial, and subepicardial areas, and draining (collecting) vessels that lead the lymph out of the heart. There are interspecies differences in the distribution of lymphatic capillaries, especially near the valves, as well as differences in the routes and number of draining vessels. In some species, subendocardial areas contain fewer lymphatic capillaries as compared to subepicardial parts of the heart. In all species there is at least one collector vessel draining lymph from the subepicardial plexuses and running along the anterior interventricular septum under the left auricle and further along the pulmonary trunk outside the heart and terminating in the right venous angle. The second collector assumes a different route in various species. In most mammalian species the collectors run along major branches of coronary arteries, have valves and a discontinuous layer of smooth muscle cells. PMID 24592145


Loss of Function of the Mouse Sharpin Gene Results in Peyer's Patch Regression

PLoS One. 2013;8(2):e55224. doi: 10.1371/journal.pone.0055224. Epub 2013 Feb 12.

Seymour R, Shirley BJ, Hogenesch H, Shultz LD, Sundberg JP. Source The Jackson Laboratory, Bar Harbor, Maine, United States of America.


Peyer's patches (PP) are an important component in the immune response against intestinal pathogens. Two independent, spontaneous mutations in the mouse Sharpin gene (Sharpin(cpdm) and Sharpin(cpdm-Dem)) result in the absence of PP and disrupted splenic white pulp in adult mice, although a full complement of lymph nodes is present. Here we report that rudimentary PP begin to develop in Sharpin(cpdm) mice during embryogenesis, but lack the organizational patterns that are typical of this tissue. In the present study, small intestines examined at weekly intervals from birth to maturity showed spontaneous regression of PP in mutant mice with concurrent infiltration of granulocytes. At 5 to 6 weeks of age, only indistinct remnants of granulocytic accumulations remain. Transplantation of normal bone marrow into Sharpin(cpdm) mice at 7 days of age did not prevent regression of PP in bone marrow chimeras examined at 7 to 8 weeks of age. These findings indicate that SHARPIN expression is required for the normal development and maintenance, but not initiation, of PP.

PMID 23424624

Regulation of lymphatic vascular morphogenesis: Implications for pathological (tumor) lymphangiogenesis

Exp Cell Res. 2013 Feb 6. pii: S0014-4827(13)00034-7. doi: 10.1016/j.yexcr.2013.01.016. [Epub ahead of print]

Martinez-Corral I, Makinen T. Source Lymphatic Development Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.


Lymphatic vasculature forms the second part of our circulatory system that plays a critical role in tissue fluid homeostasis. Failure of the lymphatic system can lead to excessive accumulation of fluid within the tissue, a condition called lymphedema. Lymphatic dysfunction has also been implicated in cancer metastasis as well as pathogenesis of obesity, atherosclerosis and cardiovascular disease. Since the identification of the first lymphatic marker VEGFR-3 and growth factor VEGF-C almost 20 years ago, a great progress has been made in understanding the mechanisms of lymphangiogenesis. This has been achieved largely through characterization of animal models with specific lymphatic defects and identification of genes causative of human hereditary lymphedema syndromes. In this review we will summarize the current understanding of the regulation of lymphatic vascular morphogenesis, focusing on mechanisms that have been implicated in both developmental and pathological (tumor) lymphangiogenesis. Copyright © 2013 Elsevier Inc. All rights reserved.

PMID 23395992


IgG placental transfer in healthy and pathological pregnancies

Clin Dev Immunol. 2012;2012:985646. Epub 2011 Oct 1.

Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. Source Departamento de Pediatria, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Enéas Carvalho de Aguiar, 647, Cerqueira César, São Paulo, SP 05403-900, Brazil.


Placental transfer of maternal IgG antibodies to the fetus is an important mechanism that provides protection to the infant while his/her humoral response is inefficient. IgG is the only antibody class that significantly crosses the human placenta. This crossing is mediated by FcRn expressed on syncytiotrophoblast cells. There is evidence that IgG transfer depends on the following: (i) maternal levels of total IgG and specific antibodies, (ii) gestational age, (iii) placental integrity, (iv) IgG subclass, and (v) nature of antigen, being more intense for thymus-dependent ones. These features represent the basis for maternal immunization strategies aimed at protecting newborns against neonatal and infantile infectious diseases. In some situations, such as mothers with primary immunodeficiencies, exogenous IgG acquired by intravenous immunoglobulin therapy crosses the placenta in similar patterns to endogenous immunoglobulins and may also protect the offspring from infections in early life. Inversely, harmful autoantibodies may cross the placenta and cause transitory autoimmune disease in the neonate.

PMID 22235228

Development of murine hepatic NK cells during ontogeny: comparison with spleen NK cells

Clin Dev Immunol. 2012;2012:759765. Epub 2011 Dec 6.

Wu X, Chen Y, Wei H, Sun R, Tian Z. Source Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, China.


The phenotype of developing liver NK cells (CD3(-)NK1.1(+)) was investigated during mouse ontogeny comparing with spleen NK cells. The highest percentage of hepatic CD27(-)CD11b(-) NK cells occurred at the fetal stage. After birth, the percentage of CD27(-)CD11b(-)NK cells in both the liver and spleen gradually decreased to their lowest level at 6 weeks. More CD27(+)CD11b(-)NK cells were detected in the liver than that in spleen from week 1 to 6. Expression of NKG2A on liver NK cells was decreased but still much higher than that of spleen NK cells after 1 week. The NKG2D expression on liver NK cells increased to its highest level and was significantly higher than on spleen NK cells till 4 weeks. During mouse ontogeny, weaker expression of NKp46 and CD2 and stronger expression of CD69, CD11c, 2B4, and CD73 were observed on liver NK cells. Furthermore, neonatal liver NK cells express higher IFN-γ and perforin than adult .These results suggest that the maturation process of NK cells is unique in the livers, and liver microenvironments might play critical roles to keep NK cells in an immature status.

  • The liver is a lymphoid organ with a predominantly innate immune system [31, 32]. NK cells are abundant in the normal liver, accounting for approximately one-third of intrahepatic lymphocytes, which differs from other lymphoid organs and peripheral blood.

PMID 22203859

31 Hepatology. 2008 Feb;47(2):729-36. Liver: An organ with predominant innate immunity. Gao B, Jeong WI, Tian Z. Source Section on Liver Biology, Laboratory of Physiologic Studies, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD 20892, USA. Abstract Blood circulating from the intestines to the liver is rich in bacterial products, environmental toxins, and food antigens. To effectively and quickly defend against potentially toxic agents without launching harmful immune responses, the liver relies on its strong innate immune system. This comprises enrichment of innate immune cells (such as macrophages, natural killer, natural killer T, and gammadelta T cells) and removal of waste molecules and immunologic elimination of microorganisms by liver endothelial cells and Kupffer cells. In addition, the liver also plays an important role in controlling systemic innate immunity through the biosynthesis of numerous soluble pathogen-recognition receptors and complement components. CONCLUSION: The liver is an organ with predominant innate immunity, playing an important role not only in host defenses against invading microorganisms and tumor transformation but also in liver injury and repair. Recent evidence suggests that innate immunity is also involved in the pathogenesis of liver fibrosis, providing novel therapeutic targets to treat such a liver disorder. PMID 18167066

Annu Rev Immunol. 2009;27:147-63. The liver as a lymphoid organ. Crispe IN. Source David H. Smith Center for Vaccine Biology and Immunology, Aab Institute for Biomedical Research, University of Rochester Medical Center, Rochester, New York 14642, USA. Abstract The liver receives blood from both the systemic circulation and the intestine, and in distinctive, thin-walled sinusoids this mixture passes over a large macrophage population, termed Kupffer cells. The exposure of liver cells to antigens, and to microbial products derived from the intestinal bacteria, has resulted in a distinctive local immune environment. Innate lymphocytes, including both natural killer cells and natural killer T cells, are unusually abundant in the liver. Multiple populations of nonhematopoietic liver cells, including sinusoidal endothelial cells, stellate cells located in the subendothelial space, and liver parenchymal cells, take on the roles of antigen-presenting cells. These cells present antigen in the context of immunosuppressive cytokines and inhibitory cell surface ligands, and immune responses to liver antigens often result in tolerance. Important human pathogens, including hepatitis C virus and the malaria parasite, exploit the liver's environment, subvert immunity, and establish persistent infection. PMID 19302037


Peyer's patches are precocious to the appendix in human development

Dev Immunol. 2001;8(2):159-66.

Bhide SA1, Wadekar KV, Koushik SA.


PP are first visible at approximately 15.5 wk gestation after which there is a rapid spurt in the development and maturation of lymphoid follicles so that at any given point of time new foci of PP development are continuously formed at a rapid rate. Addition of rows of follicles results in the formation of a PP. Immature PP of younger fetuses have a spongy structure in contrast with the compact lymphoid follicles of mature PP of older fetuses. Immunocytochemical studies reveal that there is a subtle gradation in the expression of lymphocyte surface markers with increasing fetal age. Expression of antigenic markers occurs in an ordered sequence viz. HLA - DR, CD19 (B cell population), CD9 (pre-B cells), CD3 T lymphocytes, CD4 helper / inducer lymphocytes, the CD8 suppressor / cytotoxic cells and lastly, the CD57 Natural Killer cells. The antigens are expressed first on lymphocytes of PP and thereafter in those of the appendix. Our findings clearly demonstrate that the approximately 5 wk fetal period from 17.5 wk to 22 wk represents a major growth phase in the development of surface markers of lymphocytes in the mucosal immune system of the gut. PMID 11589311 PMCID: PMC2276071

New ways to turn on NKT cells


Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans

Science. 2010 Dec 17;330(6011):1695-9.

Mold JE, Venkatasubrahmanyam S, Burt TD, Michaëlsson J, Rivera JM, Galkina SA, Weinberg K, Stoddart CA, McCune JM.

Division of Experimental Medicine, Department of Medicine, University of California, San Francisco, CA 94143-1234, USA. Erratum in:

Science. 2011 Feb 4;331(6017):534. Comment in:

Science. 2010 Dec 17;330(6011):1635-6.


Although the mammalian immune system is generally thought to develop in a linear fashion, findings in avian and murine species argue instead for the developmentally ordered appearance (or "layering") of distinct hematopoietic stem cells (HSCs) that give rise to distinct lymphocyte lineages at different stages of development. Here we provide evidence of an analogous layered immune system in humans. Our results suggest that fetal and adult T cells are distinct populations that arise from different populations of HSCs that are present at different stages of development. We also provide evidence that the fetal T cell lineage is biased toward immune tolerance. These observations offer a mechanistic explanation for the tolerogenic properties of the developing fetus and for variable degrees of immune responsiveness at birth.

PMID 21164017

Platelets: covert regulators of lymphatic development

Arterioscler Thromb Vasc Biol. 2010 Dec;30(12):2368-71. Epub 2010 Nov 11.

Bertozzi CC, Hess PR, Kahn ML. Department of Medicine and Cardiovascular Institute, University of Pennsylvania, Philadelphia Pa 19104, USA.


The field of platelet biology has rapidly expanded beyond the classical role of platelets in preventing blood loss and orchestrating clot formation. Despite the lack of transcriptional ability of these anuclear cell fragments, platelet function is now thought to encompass such diverse contexts as tissue repair, immune activation, primary tumor formation, and metastasis. Recent studies from multiple groups have turned the spotlight on an exciting new role for platelets in the formation of lymphatic vessels during embryonic development. Genetic experiments demonstrate that podoplanin, a transmembrane protein expressed on lymphatic endothelial cells, engages the platelet C-type lectin-like receptor 2 (CLEC-2) when exposed to blood, leading to SYK-SLP-76-dependent platelet activation. When components of this pathway are disrupted, aberrant vascular connections form, resulting in blood-lymphatic mixing. Furthermore, platelet-null embryos manifest identical blood-lymphatic mixing. The identification of platelets as the critical cell type mediating blood-lymphatic vascular separation raises new questions in our understanding of lymphatic development and platelet biology.

PMID 21071706


Organogenesis of lymphoid tissues

Nat Rev Immunol. 2003 Apr;3(4):292-303. Mebius RE. Source Department of Molecular Cell Biology, VU University Medical Center, v.d. Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands. Erratum in Nat Rev Immunol. 2003 Jun;3(6):509.


The development of lymphoid organs depends on the correct expression of several molecules within a defined timeframe during ontogeny. Although this is an extremely complex process, with each secondary lymphoid tissue requiring subtly different signals, a common framework for lymphoid development is beginning to emerge. Drawing on studies of lymph nodes, Peyer's patches and nasal-associated lymphoid tissue, an integrative model of lymphoid-tissue development, involving adhesion molecules, cytokines and chemokines, which emphasizes the role of interactions between CD3-CD4+CD45+ 'inducer' cells and VCAM1+ICAM1+ stromal 'organizer' cells is presented.

PMID 12669020

Morphological study of development and functional activity of palatine tonsils in embryonic age

Acta Otorhinolaryngol Ital. 2003 Apr;23(2):98-101. Noussios G, Xanthopoulos J, Zaraboukas T, Vital V, Konstantinidis I. Source Department of Otolaryngology Head and Neck Surgery, Hippokratio General Hospital, Thessaloniki, Greece.


Palatine tonsils play an important role in the development of the immune system, being the first organ in the lymph system which analyses and reacts to antigenic stimulation. In this study, the peritonsillar area of Waldeyer's ring was investigated in 88 normal human embryos which were examined histologically and immunohistochemically. The progressive development of palatine tonsils during embryonic life is discussed. The first appearance of tonsils is in about the 14th-15th week followed by a parallel development of B- and T-cell regions which accounts for the high incidence of non mucosa-associated lymphoid tissue lymphomas among all tonsillar lymphomas and the higher incidence of T-cell-lymphomas, in comparison to the mucosa-associated lymphoid tissue of the digestive system. The way in which the human body develops the palatine tonsils quickly and prepares them to react to the first antigenic stimulation, are discussed.

PMID 14526557


Phenotypic and functional analysis of human T lymphocytes in early second- and third-trimester fetuses

Clin Exp Immunol. 2002 Aug;129(2):302-8.

Zhao Y, Dai ZP, Lv P, Gao XM. Source Department of Obstetrics & Gynaecology, People's Hospital, Peking University, Beijing, China.


This study was undertaken to investigate the phenotypic and functional status of T lymphocytes of human fetuses from early second- to third-trimester. Cord blood samples were obtained from 19 healthy human fetuses (gestation weeks: 18-36), by cordocentesis, and 16 term newborns (gestation weeks 37-42). Maternal and unrelated male blood samples were also taken as controls. Percentage of lymphocytes in fetal white blood cells was 79.3%, reducing to 40% by term birth, much higher than that of adults. Cord blood mononuclear cells (CBMC), prepared by density gradient centrifugation followed by lysis of erythrocytes, were stained using PE- or FITC-labelled monoclonal Abs and analysed by flow cytometry. The frequencies of CD3+ T cells in fetal (40.1%) and neonatal (42.4%) CBMC were significantly lower than that of men (59.6%) and pregnant women (53.6%). Proportions of CD8+ T cells (9.5%), gammadelta-T cells (0.5%) and NK cells (4.8%) in fetal CBMC were also lower than that of neonates (except gammadelta-T cells) and adults. A negative linear correlation (r = -0.609) between the ratio of CD4+/CD8+ T cells in fetal blood and gestation age could also be established. Fetal CBMC showed vigorous spontaneous proliferation but failed to respond to mitogen (PHA) or allogeneic stimulation in vitro. The fetal mononuclear cells were unable to produce IL-2, IL-4 or IFN-gamma, but spontaneously secreted IL-10, IL-6 and TNF-alphain vitro. Stimulation with PHA up-regulated the production of IL-10, IL-6 and TNF-alpha substantially.

PMID 12165087


Slow, programmed maturation of the immunoglobulin HCDR3 repertoire during the third trimester of fetal life

Blood. 2001 Nov 1;98(9):2745-51.

Schroeder HW Jr, Zhang L, Philips JB 3rd. Source Division of Developmental and Clinical Immunology, Department of Medicine, University of Alabama at Birmingham, 35294, USA.


The mean distribution of lengths in the third complementarity-determining region of the heavy chain (HCDR3) serves as a measure of the development of the antibody repertoire during ontogeny. To determine the timing and pattern of HCDR3 length maturation during the third trimester of pregnancy, the mean distribution of HCDR3 lengths among variable-diversity-joining-constant-mu (VDJC(mu)) transcripts from the cord blood was analyzed from 138 infants of 23 to 40 weeks' gestation, including 3 sets of twins, 2 of which were of dizygotic origin. HCDR3 maturation begins at the start of the third trimester; follows a slow, continuous expansion over a 5-month period; and is unaffected by race or sex. The range and mean distribution of lengths may vary in dizygotic twins, indicating individual rates of development. The mean HCDR3 length distribution in 10 premature infants with documented bacterial sepsis was then followed for 2 to 12 weeks after their first positive blood culture. HCDR3 spectrotype analysis demonstrated oligoclonal B-cell activation and expansion after sepsis, but maturation of the repertoire was not accelerated even by the systemic exposure to external antigen represented by bacteremia. Antibody repertoire development appears to be endogenously controlled and adheres to an individualized developmental progression that probably contributes to the relative immaturity of the neonatal immune response.

PMID 11675347

Dynamics of immunoglobulins at the feto-maternal interface

Rev Reprod. 1999 May;4(2):81-9.

Saji F, Samejima Y, Kamiura S, Koyama M. Source Department of Gynecology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. Abstract Transplacental transport of maternal immunoglobulin G (IgG) to the developing fetus is extremely important in the protection of the newborn from infection. Although the exact mechanisms of the selective and active transfer of IgG across the placental barrier are not fully understood, receptors for the Fc part of IgG (FcgammaRs) in the placenta are believed to play a key role. Several known Fc receptors, FcgammaRI, FcgammaRII, FcgammaRIII and FcRn (neonatal FcR), demonstrate heterogeneous expression patterns in placenta. Immunohistochemical analysis shows the expression of FcgammaRI on Hofbauer cells in stromal tissue, FcbetaRII on Hofbauer cells and fetal blood endothelium, FcgammaRIII on Hofbauer cells and trophoblasts, and FcRn on syncytiotrophoblasts and endothelial cells. Recent studies provide evidence for important associations among these receptors and transcytosis of IgG, as well as scavenger mechanisms for clearing immune complexes in the placenta during pregnancy.

PMID 10357095