Abstract
Lymphoblasts from the mesenteric lymph nodes (MN) of mice home to the mammary glands of syngeneic recipients late in pregnancy and during lactation, and within hours of transfer most can be shown to contain IgA. Homing does not occur in virgins, in early pregnancy, or after weaning. Homing MN lymphoblasts are sensitive to antiserum to IgA plus complement, but not to other class-specific antisera. Thus, lymphoblasts in MN with the potential to home to the mammary gland are already committed to IgA synthesis and bear surface IgA before reaching their destination. These results explain observations, made by others, of specific IgA antibodies and IgA plasma cells in milk and colostrum after oral immunization. Under natural conditions it is likely that IgA precursor cells, after stimulation in the gut-associated lymphoid tissue by intestinal antigens, migrate to the mammary gland where they secrete antibodies which constitute an important defense mechanism of the newborn. In the absence of lactation, these cells probably form part of the normal traffic to the lamina propria of the small intestine.
Full Text
The Full Text of this article is available as a PDF (824.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Allardyce R. A., Shearman D. J., McClelland D. B., Marwick K., Simpson A. J., Laidlaw R. B. Appearance of specific colostrum antibodies after clinical infection with Salmonella typhimurium. Br Med J. 1974 Aug 3;3(5926):307–309. doi: 10.1136/bmj.3.5926.307. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ammann A. J., Stiehm E. R. Immune globulin levels in colostrum and breast milk, and serum from formula- and breast-fed newborns. Proc Soc Exp Biol Med. 1966 Aug-Sep;122(4):1098–1100. doi: 10.3181/00379727-122-31335. [DOI] [PubMed] [Google Scholar]
- Behrens M. M., Inman J. K., Vannier W. E. Protein-cellulose derivatives for use as immunoadsorbents: preparation employing an active ester intermediate. Arch Biochem Biophys. 1967 Mar;119(1):411–419. doi: 10.1016/0003-9861(67)90472-9. [DOI] [PubMed] [Google Scholar]
- Bianco C., Patrick R., Nussenzweig V. A population of lymphocytes bearing a membrane receptor for antigen-antibody-complement complexes. I. Separation and characterization. J Exp Med. 1970 Oct 1;132(4):702–720. doi: 10.1084/jem.132.4.702. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cebra J. J., Gearhart P. J., Kamat R., Robertson S. M., Tseng J. Origin and differentiation of lymphocytes involved in the secretory IgA responses. Cold Spring Harb Symp Quant Biol. 1977;41(Pt 1):201–215. doi: 10.1101/sqb.1977.041.01.026. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crabbé P. A., Nash D. R., Bazin H., Eyssen D. V., Heremans J. F. Antibodies of the IgA type in intestinal plasma cells of germfree mice after oral or parenteral immunization with ferritin. J Exp Med. 1969 Oct 1;130(4):723–744. doi: 10.1084/jem.130.4.723. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Craig S. W., Cebra J. J. Peyer's patches: an enriched source of precursors for IgA-producing immunocytes in the rabbit. J Exp Med. 1971 Jul 1;134(1):188–200. doi: 10.1084/jem.134.1.188. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Diaz-Jouanen E., Williams R. C., Jr T and B lymphocytes in human colostrum. Clin Immunol Immunopathol. 1974 Nov;3(2):248–255. doi: 10.1016/0090-1229(74)90011-7. [DOI] [PubMed] [Google Scholar]
- Goldblum R. M., Ahlstedt S., Carlsson B., Hanson L. A., Jodal U., Lidin-Janson G., Sohl-Akerlund A. Antibody-forming cells in human colostrum after oral immunisation. Nature. 1975 Oct 30;257(5529):797–798. doi: 10.1038/257797a0. [DOI] [PubMed] [Google Scholar]
- Guy-Grand D., Griscelli C., Vassalli P. The gut-associated lymphoid system: nature and properties of the large dividing cells. Eur J Immunol. 1974 Jun;4(6):435–443. doi: 10.1002/eji.1830040610. [DOI] [PubMed] [Google Scholar]
- Guyer R. L., Koshland M. E., Knopf P. M. Immunoglobulin binding by mouse intestinal epithelial cell receptors. J Immunol. 1976 Aug;117(2):587–593. [PubMed] [Google Scholar]
- Hall J. G., Hopkins J., Orlans E. Studies on the lymphocytes of sheep. III. Destination of lymph-borne immunoblasts in relation to their tissue of origin. Eur J Immunol. 1977 Jan;7(1):30–37. doi: 10.1002/eji.1830070108. [DOI] [PubMed] [Google Scholar]
- Holmgren J., Hanson L. A., Carlson B., Lindblad B. S., Rahimtoola J. Neutralizing antibodies against Escherichia coli and Vibrio cholerae enterotoxins in human milk from a developing country. Scand J Immunol. 1976;5(6-7):867–871. doi: 10.1111/j.1365-3083.1976.tb03036.x. [DOI] [PubMed] [Google Scholar]
- Jones P. P., Cebra J. J. Restriction of gene expression in B lymphocytes and their progeny. III. Endogenous IgA and IgM on the membranes of different plasma cell precursors. J Exp Med. 1974 Oct 1;140(4):966–976. doi: 10.1084/jem.140.4.966. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kagnoff M. F. Functional characteristics of Peyer's patch lymphoid cells. IV. Effect of antigen feeding on the frequency of antigen-specific B cells. J Immunol. 1977 Mar;118(3):992–997. [PubMed] [Google Scholar]
- Kleinberg D. L., Frantz A. G. Human prolactin: measurement in plasma by in vitro bioassay. J Clin Invest. 1971 Aug;50(8):1557–1568. doi: 10.1172/JCI106643. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lamm M. E. Cellular aspects of immunoglobulin A. Adv Immunol. 1976;22:223–290. doi: 10.1016/s0065-2776(08)60550-7. [DOI] [PubMed] [Google Scholar]
- Lobo P. I., Westervelt F. B., Horwitz D. A. Identification of two populations of immunoglobulin-bearing lymphocytes in man. J Immunol. 1975 Jan;114(1 Pt 1):116–119. [PubMed] [Google Scholar]
- Love R. J., Ogilvie B. M. Nippostrongylus brasiliensis and Trichinella spiralis: localization of lymphoblasts in the small intestine of parasitized rats. Exp Parasitol. 1977 Feb;41(1):124–132. doi: 10.1016/0014-4894(77)90138-2. [DOI] [PubMed] [Google Scholar]
- Mandel M. A., Asofsky R. Studies of thoracic duct lymphocytes of mice. I. Immunoglobulin synthesis in vitro. J Immunol. 1968 Feb;100(2):363–370. [PubMed] [Google Scholar]
- McWilliams M., Lamm M. E., Phillips-Quagliata J. M. Surface and intracellular markers of mouse mesenteric and peripheral lymph node and Peyer's patch cells. J Immunol. 1974 Oct;113(4):1326–1333. [PubMed] [Google Scholar]
- McWilliams M., Phillips-Quagliata J. M., Lamm M. E. Characteristics of mesenteric lymph node cells homing to gut-associated lymphoid tissue in syngeneic mice. J Immunol. 1975 Jul;115(1):54–58. [PubMed] [Google Scholar]
- McWilliams M., Phillips-Quagliata J. M., Lamm M. E. Mesenteric lymph node B lymphoblasts which home to the small intestine are precommitted to IgA synthesis. J Exp Med. 1977 Apr 1;145(4):866–875. doi: 10.1084/jem.145.4.866. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Montgomery P. C., Rosner B. R., Cohn J. The secretory antibody response. Anti-DNP antibodies induced by dinitrophenylated type 3 pneumococcus. Immunol Commun. 1974;3(2):143–156. doi: 10.3109/08820137409055752. [DOI] [PubMed] [Google Scholar]
- Parmely M. J., Beer A. E., Billingham R. E. In vitro studies on the T-lymphocyte population of human milk. J Exp Med. 1976 Aug 1;144(2):358–370. doi: 10.1084/jem.144.2.358. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parrott D. M., Ferguson A. Selective migration of lymphocytes within the mouse small intestine. Immunology. 1974 Mar;26(3):571–588. [PMC free article] [PubMed] [Google Scholar]
- Pierce N. F., Gowans J. L. Cellular kinetics of the intestinal immune response to cholera toxoid in rats. J Exp Med. 1975 Dec 1;142(6):1550–1563. doi: 10.1084/jem.142.6.1550. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rose M. L., Parrott D. M., Bruce R. G. Migration of lymphoblasts to the small intestine. II. Divergent migration of mesenteric and peripheral immunoblasts to sites of inflammation in the mouse. Cell Immunol. 1976 Nov;27(1):36–46. doi: 10.1016/0008-8749(76)90151-9. [DOI] [PubMed] [Google Scholar]
- Rudzik R., Clancy R. L., Perey D. Y., Day R. P., Bienenstock J. Repopulation with IgA-containing cells of bronchial and intestinal lamina propria after transfer of homologous Peyer's patch and bronchial lymphocytes. J Immunol. 1975 May;114(5):1599–1604. [PubMed] [Google Scholar]
- Stoliar O. A., Pelley R. P., Kaniecki-Green E., Kkaus M. H., Carpenter C. C. Secretory IgA against enterotoxins in breast-milk. Lancet. 1976 Jun 12;1(7972):1258–1261. doi: 10.1016/s0140-6736(76)91735-9. [DOI] [PubMed] [Google Scholar]
- Uhr J. W., Vitetta E. S. Cell surface immunoglobulin. 8. Synthesis, secretion, and cell surface expression of immunoglobulin in murine thoracic duct lymphocytes. J Exp Med. 1974 Apr 1;139(4):1013–1018. doi: 10.1084/jem.139.4.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams A. F., Gowans J. L. The presence of IgA on the surface of rat thoractic duct lymphocytes which contain internal IgA. J Exp Med. 1975 Feb 1;141(2):335–345. doi: 10.1084/jem.141.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Winchester R. J., Fu S. M., Hoffman T., Kunkel H. G. IgG on lymphocyte surfaces; technical problems and the significance of a third cell population. J Immunol. 1975 Apr;114(4):1210–1212. [PubMed] [Google Scholar]