Talk:Paper - The first lymph glands in rabbits and human embryos (1909)

From Embryology

The First Lymph Glands Ix Rabbit And Human Embryos


Fredekic T. Lewis. Assistant Profctssor of Emhryology at the Harvard Medical School

lu 181)6 Sapcer stated that the lymph glands in sheep and cow embryos arise from a plexus of lymphatic vessels.^ "The connectivetissue between the lymphatic vessels of the plexus has at first a trabecular arrangement, but later one or more compact masses or islands are formed within it. From the beginning, the connective tissue which makes the trabeculae, or masses, is narrower meshed than that which surrounds it, and contains many blood vessels. However, he adds : "There can be no doubt that there are many plexus formations in embryonic tissue, having exactly the appearance of those from which lymph glands arise, which simply degenerate."

Kling, in 1904, emphasized the importance of the plexus stage and modelled the lymphoid trabeculae.^ Although they connect with one another so as to form a continuous mass, his model has "an extremely irregular appearance." It shows that these structures have little resemblance to the future glands. Kling stated that from such a general mass portions were separated by constriction to form the basis for individual glands. But "lymph glands which have an isolated position appear from the first as solitary formations; each one arises independently."

A year later Miss Sabin wrote:' "All of the nodes of the early

'Saxer, F., I'eher die Entwickelung iiiid deii Bau der noriiialeii Lyiiii)hdrliseii. Anat. Ilefte, 1800, vol. G, pp. .'U9-.5.32.

'KHng, C. A., Studien ilber die Entwicklung der LympbdrilRen beiiii Menschen. Arch. f. mikr. Anat, 1904. vol. e.3, pp. 575-010.

•Sabin, F. R., The development of the lymphatic nodes in the pig and their relation to the lymph hearts. Amer. .Tourn. of Anat., 1905, vol. 4, pp. 855-389.


D 342 Frederic T. Txnvis.

embryos, the primary nodes in the sense of GuUand, pass through this (plexus) stage. Lymphatic nodes which develop later in the life of the embry'o, after lymphocytes occur, hurry through the primary process and show a considerable modification of it." Recently* Dr. Sabin published the figure of a section through the jugular lymph sac in a human embryo of 30 mm., "to show the simple bridging of the sac which is the anlage of the first lymph node." In the pig she found that "the first node to appear develops from the lymph heart, which is in the supra-clavicular triangle behind the sternocleidomastoid muscle."

Thus, Saxer, Kliug and ^liss Sabin agree that the first lymph glands arise from trabeculac in a plexus of lymphatic vessels.

The plexus of lymphatics in relation with the internal jugular vein is a conspicuous feature in human embryos measuring from 30 to 40 mm. It is shown in Figs. 1 and 2 from an embryo of 42 mm. A portion of the vein is seen in the lower right corner of each photograph, in places the connective tissue trabeculae arc broad and pale, as shown in Fig. 1. Elsewhere they are more slender and deeply staining, as in the left part of Fig. 1 and in Fig. 2. The latter is a section through the structure which Miss Sabin has described as the primary lymph gland.

The cells in the similar trabeculae of a 31 mm. human embryo are described by Kling as having "chiefly, if not exclusively, the char

Sablii, F. R., The lymphatic system In human embryos, with a consideration of the morphology of the system as a whole. Amer. Journ. of Anat., 1{K)9, vol. 9, pp. 43-91.


Figs. 1 and 2. — Plexus of lymphatic vessels in relation with tlie internal jugular vein. From a human embryo of 42 mm. X 45 diams. (Harvard Fmbryological Colleetio;i, Series 841, Section 432, and Series 838, Section 153, respectively).

Figs. 3, 4, and 5. — Lymi)h glands from a human embryo of 42 mm. X 60 diams. Fig. 3 shows the submental ("submaxillary*') gland (Series 841, Section 5S9) ; Fig. 4 shows the external jugular gland (Series 841, Section 524) ; and Fig. 5. the circumflex scapular gland (Series 8J58, Section 321).

Fig. G. — Sul)scai)ular lymph gland from a rabbit of 20 days, 29 mm. X 60 diams. (II. K. C, Series 170, Section lOSO.)

D Fir.. 1.

Fig. 2.

Fio. 3.

Fig. 4.

Fig. 5,

Fig. 6.

D .344 Frederic T. Ix^wis.

acter of fixed connective tissue cells." At 70 mm. *Ve find among pale oval nuclei, others of rounder form and darker stain which already suggest adenoid tissue." Similarly, in pigs of 80 mm. Miss Sabin found large, faintly staining, oval nuclei belonging to connective tissue, and small, round, deeply staining nuclei with coarser chromatin granules and a more distinct membrane, which belong to lymphocytes. '^Between the connective tissue cell, especially the young forms, and the lymphocyte one can see every possible transition" (1905, p. 371). Saxer likewise found that '^the lymphocytes, which later form the bulk of the lymph glands, arise in loco."

The examination of the bridges in the 42 mm. embryo shows the pale oval cells and the darker round ones apparently derived from them, and indicates that these trabeculae contain lymphoid tissue. They do not, however, constitute a lymph gland, but represent the material from which the chain of deep cervical lymph glands is to be derived. A sufficiently detailed study of the later stages of the plexus has not yet been made. Bonnot' believes that it produces the "interscapular gland" of Ilatai, which seems to be a collective term for the cervical fat and lymph glands.

Almost simultaneously with the lymphoid transformation of trabeculae among the jugular lymphatics, distinct lymph glands appear in the superficial tissues. These do not pass through a plexus stage, but from the first they resemble the glands of the adult. The striking diiference in the arrangement of the deep and the superficial lymphoid tissue seems due to the fact that the deep tissue is molded about an involved pre-existing plexus; but the superficial glands develop freely in the loose subcutaneous tissue. The plexus stage may therefore be regarded as a complication in the development of the glands, rather than a fundamental condition which is sometimes hurried through, modified, or omitted.

In the human embryo of 42 mm. two superficial glands were found on either side of the head. Their position is indicated in Fig. 7. The smaller gland is in intimate relation with the submental branch of the anterior facial vein. A section through it is shown in Fig. 8.

•Bonnot, E.. Tlie interscapular gland. Journ. of Anat. and Phys., 1908, vol. 43, pp. 43-58.

D Lymph Glands in Kabbit and Human Embryos.


At the upper border of the photograph a part of Meckel's cartilage is seen on the left, and the bone of the lower jaw on the right ; the lower border of the photograph passes through the submaxillary gland. Between the submaxillary gland and the mandible the submental vein appears, surrounded by dense tissue. This dense lymphoid tissue is chiefly on the upper side of the vein, and it is bounded by a lymphatic

Fig. 7

Fig. 7. — The head of a human embryo of 42 mm., to show the position of the submental ("submaxiUary") and external jugular glands. X 2-2/5 diams. (H. E. C, 841.)

Fig. 8. — The head of a rabbit embryo of 29 mm. to show the position of the IKisterlor facial gland. X 4 diams. (II. E. C, 170.)

The veins shown are the anterior and posterior facial, the linguo-facial, the external and internal jugular, and the jugulo-cephallc. (The external jugular of man corresponds with the jugulo-cephallc of the rabbit and not with the linguo-facial ; the latter in the rabbit is, however, usually called the external jugular. Cf. I^ewis, Amer. Journ. of Anat., vol. 9, p. 33.)

vessel, crescentic in section. The submental vein sends branches into and through the lymph gland.

The other lymph gland in the head is in relation with the external jugular vein. It is shown in section in Fig. 4. Lymphoid tissue, enclosing small blood vessels, forms a rounded mass attached to the lower part of the vein. Its free surface is in relation with a crescentic lymph sinus. No other lymph glands were found in the head of this embryo.

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Frederic T. Lewis.

In a human embryo of 30 mm. the submental® and external jugular glands were not found. They are not mentioned in four embryos of 46-50 mm. described by Miss Sabin, but she has recorded that in an

Fig. 9. — Keconstructlon of the arteries In the axilla of the human embryo of 42 mm., to show the position of the first axillary lymph gland. X 10 dianis. (H. E. C, 838). The subscapular branch of the axillary artery is seen to divide into the circumflex scapular and thoraco-dorsal arteries. The lymph gland is along the latter. The brachial and lateral thoracic arteries are also shown:

80 mm. embryo "there are secondary lymph nodes along the veins of the neck; for example, along the external jugular vein next the parotid gland and along the facial vein at the angle of the jaw."

•It seems desirable to name the early lymph glands for the veins which they accompany and this has been done. It is to be noted, however, that in the adult there are several glands along the submental vessels, the anterior ones forming the submental group, and the posterior ones the submaxUlary group. The submental gland of the 42 mm. embryo belongs evidently with the submaxillary group of the adult.

D Lymph Glands in Rabbit and Human Embryos. 34:7

Since the early lymph glands develop with such regularity in the rabbit, it seems quite possible that these glands noted in human embryos of 80 mm. are the ones appearing at 42 mm.

The Harvard collection includes three rabbits of 29 mm. (20 days) cut in the transverse, sagittal and frontal planes respectively.

Fio. 10. — A, reconstruction of the arteries in the axilla of the 20 mm. rabbit, to show the position of the first axillary lymph gland. X 10 diams. (11. E. C, Series 170). B, reconstruction of the arteries in the pelvis of the same embryo, to show the first pelvic gland. X 10 diams.

The arteries labelled are the axillary, brachial, subscapular, aorta, iliolumbar and hypogastric.

These embryos all show a lymph gland near the junction of the anterior and posterior facial veins (Fig. 8). Except at this point, no lymph glands were found in the head.

The most distinct lymph gland in the body, in these rabbits and in the human embryo of 42 mm., is in the axillarv rcffion. In the human embryo it is an accumulation of lymphoid tissue surrounding

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Frederic T. Lewis.

the circumflex scapular artery and vein, and forming a lenticular mass bulging into the accompanying lymphatic vessel. Its position is shown in Fig. 9, and a section through it is photographed in Fig. 5. It lies next the muscle in the deep subcutaneous tissue. This gland was not found in a 30 mm. embryo, although at that stage the circumflex scapular vessels are accompanied by lymphatics. It is not specifically mentioned by Miss Sabin, and if it occurred in the embryos studied by Kling it was overlooked. At 70 mm. he found all of the axillary groups represented except the subscapular group

(p. r,88).





Fig. 11. — Wax reconstruction of the bmnan axillary gland shown In Figs. 5 and 9. X 40 dianis. A, dr. s<\ V. cit\ sc, circumflex scapular artery and vein; x. y. z., small bIo(Kl vessels, of which j? is so surrounded by lymphatic vessels, V. Jym., that it seems to perforate them; L.-gh, L.-gV,, nodules of lymphoid tissue.

A corresponding gland occurs in rabbit- embryos. It can be identified in a specimen measuring 25 mm. (18 days), and it is well defined in all three of the 20 mm. embryos. It is in relation with the subscapular vessels, which are relatively large in the rabbit (Fig. 10.4). A section through the gland is shown in Fig. 6.

Since the axillary glands seem to be the largest and most clearly defined, they were reconstructed in wax. The gland in the human embryo is shown in Fig. 11. Along the toj) of the model the circumflex scapular artery and vein pursue a parallel course, accompanied by the lymphatic vessels, V. lym. As the blood vessels approach the gland the mesenchyma around them becomes condensed and forms an intensely staining mass of lymphoid tissue, Ij-gV. Both artery and

D Lymph Glands in Rabbit and Human Embryos. 349

vein are surrounded by this tissue, but the vein seems more deeply embedded. The lymphoid tissue extends for some distance along these vessels and forms a second nodular swelling, L.-gL The position of these swellings may be determined by the small branches of the blood vessels, y and 2;, which they accompany. The main mass of lymphoid tissue, L.-gL, forms a lenticular nodule bulging into the perivascular lymphatic; it has been exposed by removing a part of the wall of the lymphatic vessel. In the photograph, Fig. 5, the dark

Fio. 12. — Wax reconstruction of the axillary gland of the rabbit shown in Figs. 6 and 10 A. X 56 diams. A. subsc, V. subsc, subscapular artery and vein; V. lym., perivascular lymphatics; L. gl., lymph gland; a, &, c, d, the blood vessels correspondingly lettered in Fig. 10 A.

oval area is L,-gL of the model, and the somewhat triangular mass above it is L-gt; in the midst of the latter the vessel z may be seen. Fig. 5 is therefore a horizontal section of the model. The fact that there are two nodular masses of lymphoid tissue connected with one another suggests the twin glands (Zwillingsdriisen) which Kling regarded as malformations due to incomplete subdivision. The bulging of the lymph gland L,-gl. into the lymphatic vessel recalls the following obser\ation by Ranvier :^ "Whenever I have observed a vascular nodule on a lymphatic, the latter has appeared to be interrupted.

^Ranvier, L., Morphologie et d^veloppement du syst^me lymphatlque. ArHi. d'anat. mlc, 1807, vol. 1, pp. 137-152.

D 350 Frederic T. Ixjwis.

. . . . Thus, the lymphatic, divided at the level of the nodide, forms two trunks, of which, the inferior becomes an afferent and the superior an efferent. If a new gland forms along the course of the efferent the latter will become the afferent for the second gland. The efferent for one gland may be the afferent for another."

The subscapular gland of the rabbit is shown in the model, Fig. 12. The subscapular vein and artery are spun about with perivascular lymphatics, which extend along the branches of the blood vessels, a, b, c and d. (Compare with Fig. lOA.) The lymph gland L,-gl. is seen through a window cut in the lymphatic vessel. It rests upon the subscapular vein and bulges into the lymphatic, pushing the endothelium before it. That the gland is more intimately related to the vein than to the artery is shown in Fig. G. The upper portion of the gland is irregularly subdivided, so that in one or two sections there is a suggestion of the plexus formation ; lower down it forms a single rounded mass.

In addition to the well-defined gland in each axilla, other glands were found in the thoracic region of both the human and rabbit embryos. In the human embryo there is indication of lymphoid tissue along the dorsalis scapulae vessel and a somewhat diffuse gland near the anterior end of the internal mammary vein. Where the pleuropericardial septum joins the diaphragm a branch of the internal mammary vein passes inward, accompanied by a large lymphatic. !N^ear the junction of the septum and diaphragm lymphoid tissue is found in relation with these vessels. The left pleuro-pericardial septum is thinner and farther from the median line than the right and has no corresponding lymphoid tissue. In the rabbit there is a developing gland along the thoraco-epigastric, or external mammary vein, nearly opposite the elbow.

The glands of the head and thorax have now been described; the abdominal and pelvic regions remain to be considered. In four rabbit embryos of 29 mm. a gland was found along the ilio-lumbar vein on either side of the body. It appears to be smaller than the axillary gland, but has essentially the same features. It is more deeply placed than the other glands. The ilio-lumbar vessels (Fig. 105) have extensive subcutaneous branches, /, /, f, and a branch, e, to the abdominid

D Lymph Glands in Eabbit and Human Embryos. 351

musculature. As noted by Krause, the ilio-lumbar vessels are highly developed in the rabbit. The lymph gland is found, as shown in Fig. IOjB^ where the subcutaneous branches join the main stem.

In the abdominal part of the human embryo of 42 mm. no distinct glands were found, but along the femoral vessels, in the inguinal region, there is a suggestion of lymphoid tissue. At 50 mm. Miss Sabin describes the posterior lymph sacs as lying in the side of the pelvis opposite the first three sacral vertebrae, and states that "the entire dorsal wall of the sac is occupied by a lymph node" (1909, p. 87). A gland which extends over three sacral vertebrae is clearly unlike any gland in the adult. The structure referred to seems to be the plexus of deep lymphatics, among which lymphoid tissue has appeared, but has not yet formed glands. At this stage Miss Sabin speaks of "secondary nodes" developing near the sacs along the femoral and sciatic groups of veins. In an 80 mm. embryo she describes a true lymph gland which, from its structure and position, as shown in a figure, strikingly suggests the ilio-lumbar gland of the rabbit ; it is not stated along what vessels it occurs. The description of the gland is as follows : "In Fig. 19 is a tiny lymph node . . . which illustrates well the simplest form of a lymph node, a central mass of lymphocytes with a plexus of lymph ducts around it. This plexus of ducts is so close that it may already be termed a sinus, so that the node consists of a single follicle with its peripheral sinus." It may be noted that Miss Sabin has figured such a simple gland in the lung of an adult pig (1905, p. 885), and Kling has described them in the axilla of an adult man.

From the preceding study the conclusion may be drawn that the first definite lymph glands are superficial. They appear with surprising regularity, as shown by comparing the three rabbit embryos of 29 mm. They are situated along the large cutaneous veins, and there is a well-developed pair for the head, thorax, and abdomen respectively. In addition to these, the rabbit embryo of 29 mm. gives evidence of gland formation along the thoraco-epigastric vein. The human embryo of 42 mm. differs from the rabbit of 29 mm. by the absence of the ilio-lumbar gland and the presence of the submental gland, together with indications of glands along the internal mam

D 352 Frederic T. Lewis.

mary and femoral veins. Doubtless, both in man and the rabbit the development of additional glands proceeds rapidly.

At the time when the superficial glands are distinct the deep ones are^ represented by lymphoid trabeculae, which are said to be transformed into chains of glands by the accumulation of the lymphoid tissue in nodules. Something of this sort must occur, but models showing the development of such a chain have not yet been made. It seems undesirable to speak of an extensive plexus of lymphatic vessels, even when associated with diffuse lymphoid tissue, as a lymph gland.

At the time when the lymph glands and trabeculae arise — that is, in the embryos which have now been described — there is apparently no lymphoid tissue elsewhere in the body. The spleen is well developed, but the compact tissue of which it is composed does not appear like that of the lymph glands. The thymus at this stage, in the rabbit at least, is clearly an epithelial organ. This is contrary to the statement of GuUand,^ that ^^the thymus in mammalian embryos is the first place where true adenoid tissue is formed, and it is an active center for the production of leucocytes long before lymphatic glands are formed at all.

The question of the origin of lymphocytes can be answered only by examining thin and specially stained sections. The embryos here described were prepared for general study, and the sections are 10 microns or more in thickness. They suggest, however, that the lymphocytes are forming in the glands and that they are absent from the blood. Maximow, who has studied the embr^^onic development of the blood with faultless technique, has unfortunately not examined the earliest lymph glands.® He considers that "the first leucocytes, the lymphocytes, arise at the same time and from the same source as the primitive erythroblasts. The latter represeat a specially differentiated form of cell, but the lymphocytes always remain undifferentiated.

"GuHaud, G. L., The development of lymphatic glands. Journ. of Path, and Bact., 1894, vol. 2, pp. 447-485.

•Maxinow, A., Untersuchung Uber Blut und Bhidegewebe. I. Die frflhesten EntwickluDgsstadlen dcr Blut, etc. Arch. f. mik. Anat, 1909, vol. 7H, pp. 444-561.

Digitized, by

Lymph Glands in Rabbit and Human Embryos. 363

Therefore, like the primitive blood cells from which they directly proceed, they are undifferentiated rounded amoeboid mesenchymal cells." He states that these lymphocytes of the embryo "have nothing to do with lymphoid tissue" — ^they develop in the yolk sac.

The lymphocytes of the lymph glands are, indeed, round mesenchymal cells, but, except for an occasional cell in the lymph sinus, apparently detached from the gland, they are unlike the forms of corpuscles in the adjacent vessels. It seems probable that the lymph glands, arising in rabbit embryos of 25-30 mm. and in human embryos of 30-45 mm., are the source of a special form of round mesenchymal cell, which is the true lymphocyte. This opinion can be established or disproved only by a cytological study of the early lymph glands, the position of which has been indicated.