The Journal of Immunology, Vol 142, Issue 8 2647-2653, Copyright © 1989 by American Association of Immunologists

ARTICLES

Estrogen induces normal murine CD5+ B cells to produce autoantibodies

S Ansar Ahmed, MJ Dauphinee, AI Montoya and N Talal
University of Texas Health Science Center, Department of Medicine, San Antonio 78284.

Females have better humoral immune responses and are more susceptible to autoimmune diseases than males. Normal female mice (C57BL/6J, C3H/HeJ, and NZW) have significantly increased spontaneous autoimmune plaque-forming cells (APFC) to mouse erythrocytes pretreated with bromelain (Br-ME) in spleen, peritoneal exudate cell, and bone marrow compared to their male counterparts. A minor subpopulation of B cells, CD5+ B, is thought to produce this autoantibody. As determined by dual color flow cytometry, increased APFC to Br-ME in females is not due to quantitative increase of CD5+ B cells. Rather, it is due to increased numbers or percentages) of CD5+ B cells producing these autoantibodies, because CD5+ B cells from females produced greater numbers of APFC to Br-ME than equal numbers of cells derived from males. The increased autoantibody production in females can be attributed to the effect of estrogen on the immune response because this hormone markedly augments APFC to Br-ME in intact or orchidectomized males. Male hormone had little effect. Importantly, estrogen did not increase the numbers of B or CD5+ B cells but augmented the ability of B cells to produce this response. This was verified when a T cell-depleted B cell fraction or fluorescence-activated cell sorter purified CD5+ B cells from estrogen- treated mice proved more efficient in the production of APFC to Br-ME. These results suggest that the number of CD5+ B cells committed to produce autoantibodies to Br-ME is increased under the influence of estrogen. This is the first demonstration that estrogen can augment the production of natural autoantibodies in normal mice. The overall augmented humoral immune responses in females and the B cell hyperactivity in female predominant autoimmune diseases appears to be due to estrogen.

This article has been cited by other articles:

				A. Hever, R. B. Roth, P. Hevezi, M. E. Marin, J. A. Acosta, H. Acosta, J. Rojas, R. Herrera, D. Grigoriadis, E. White, et al. Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator PNAS, July 24, 2007; 104(30): 12451 - 12456. [Abstract] [Full Text] [PDF]

				E. Karpuzoglu, J. B. Fenaux, R. A. Phillips, A. J. Lengi, F. Elvinger, and S. Ansar Ahmed Estrogen Up-Regulates Inducible Nitric Oxide Synthase, Nitric Oxide, and Cyclooxygenase-2 in Splenocytes Activated with T Cell Stimulants: Role of Interferon-{gamma} Endocrinology, February 1, 2006; 147(2): 662 - 671. [Abstract] [Full Text] [PDF]

				R. Mo, J. Chen, A. Grolleau-Julius, H. S. Murphy, B. C. Richardson, and R. L. Yung Estrogen Regulates CCR Gene Expression and Function in T Lymphocytes J. Immunol., May 15, 2005; 174(10): 6023 - 6029. [Abstract] [Full Text] [PDF]

				H. Yurino, S. Ishikawa, T. Sato, K. Akadegawa, T. Ito, S. Ueha, H. Inadera, and K. Matsushima Endocrine Disruptors (Environmental Estrogens) Enhance Autoantibody Production by B1 Cells Toxicol. Sci., September 1, 2004; 81(1): 139 - 147. [Abstract] [Full Text] [PDF]

				N. Ishimaru, R. Arakaki, M. Watanabe, M. Kobayashi, K. Miyazaki, and Y. Hayashi Development of Autoimmune Exocrinopathy Resembling Sjogren's Syndrome in Estrogen-Deficient Mice of Healthy Background Am. J. Pathol., October 1, 2003; 163(4): 1481 - 1490. [Abstract] [Full Text] [PDF]

				G. Mor, E. Sapi, V. M. Abrahams, T. Rutherford, J. Song, X.-Y. Hao, S. Muzaffar, and F. Kohen Interaction of the Estrogen Receptors with the Fas Ligand Promoter in Human Monocytes J. Immunol., January 1, 2003; 170(1): 114 - 122. [Abstract] [Full Text] [PDF]

				E. Cavalieri, K. Frenkel, J. G. Liehr, E. Rogan, and D. Roy Chapter 4: Estrogens as Endogenous Genotoxic Agents--DNA Adducts and Mutations J Natl Cancer Inst Monographs, July 1, 2000; 2000(27): 75 - 94. [Abstract] [Full Text] [PDF]

				S. M. Palmer, G. S. Gilkeson, and D. S. Pisetsky Effect of Sex on the Induction of Anti-DNA Antibodies in Normal Mice Immunized with Bacterial DNA Lupus, August 1, 1993; 2(4): 251 - 255. [Abstract] [PDF]

				S. M. Palmer, G. S. Gilkeson, and D. S. Pisetsky Effect of Sex on the Induction of Anti-DNA Antibodies in Normal Mice Immunized with Bacterial DNA Lupus, January 1, 1993; 2(1_suppl): 251 - 255. [Abstract] [PDF]