The Journal of Immunology, Vol 144, Issue 7 2529-2534, Copyright © 1990 by American Association of Immunologists

ARTICLES

IgG1 and IgG2a production by autoimmune B cells treated in vitro with IL-4 and IFN-gamma

DM Klinman
Center for Biologics Research and Evaluation, Food and Drug Administration, Bethesda, MD 20892.

Autoimmune MRL-lpr/lpr and NZB/W mice spontaneously secrete large quantities of pathogenic IgG1 and IgG2a autoantibodies. NZB mice also produce autoantibodies but these tend to be of the IgM H chain class. This work examines whether differences in the isotype of autoantibody produced by lupus-prone mice reflects differences in the sensitivity of autoreactive B cells to lymphokine-mediated IgG secretion. Twenty-five percent of normal BALB/c B cells produced IgG1 when stimulated in vitro with IL-4 plus LPS. This was comparable with the effect of IL-4 on small resting B cells from MRL-lpr/lpr and NZB/W mice. In contrast, less than 8% of the resting B cells from NZB mice produced IgG1 under these conditions. LPS plus IFN-gamma induced 5% of BALB/c and NZB/W but only 1% of NZB B cells to secrete IgG2a. Because lymphocytes from both young and old NZB mice showed diminished IgG1 and IgG2a secretion after lymphokine treatment, B cells from this strain appeared to be intrinsically resistant to the effects of IL-4 and IFN-gamma. In contrast, a disproportionately large proportion (22%) of B cells from adult MRL-lpr/lpr mice produced IgG2a when treated with IFN-gamma in vitro. Only B cells from MRL-lpr/lpr mice with active disease responded with such high levels of IgG2a production: cells from animals that had not yet developed clinical disease produced normal levels of IgG2a. Within each strain, B cells producing antibodies against autoantigens such as DNA, bromelain-treated mouse RBC and Sm responded to treatment with IL-4 and IFN-gamma in a manner indistinguishable from B cells producing antibodies against conventional Ag such as TNP and ARS.

This article has been cited by other articles:

				G. Clydesdale, J. Pekin, S. Beaton, R. J Jackson, S. Vignarajan, and C. M Hardy Contraception in mice immunized with recombinant zona pellucida subunit 3 proteins correlates with Th2 responses and the levels of interleukin 4 expressed by CD4+ cells Reproduction, December 1, 2004; 128(6): 737 - 745. [Abstract] [Full Text] [PDF]

				M. L. Gonzalez and F. J. Waxman Glomerular Deposition of Immune Complexes Made with IgG2a Monoclonal Antibodies J. Immunol., January 15, 2000; 164(2): 1071 - 1077. [Abstract] [Full Text] [PDF]

				H. Fukuyama, M. Adachi, S. Suematsu, K. Miwa, T. Suda, N. Yoshida, and S. Nagata Transgenic Expression of Fas in T Cells Blocks Lymphoproliferation But Not Autoimmune Disease in MRL-lpr Mice J. Immunol., April 15, 1998; 160(8): 3805 - 3811. [Abstract] [Full Text] [PDF]