B cells from autoimmune BXSB mice are hyporesponsive to signals provided by CD4+ T cells.
Male BXSB mice, unlike female BXSB mice, develop an early-onset, lupus-like disease characterized by high levels of anti-nuclear antibodies (Abs) and total Ig. It has recently been shown that the male BXSB mice contain an expanded population of large B cells which are hyperresponsive to stimulation by anti-CD40 mAb. The present study was undertaken to determine whether their potential for extra CD40 signaling enabled the B cells from male BXSB mice to hyper-respond to CD40L-expressing CD4+ T cells. In contrast to expectations, large B cells from male BXSB mice did not interact with CD4+ T cells in a positive manner; cultures of B cells from antigen (Ag)-primed male BXSB mice, unlike cultures of B cells from Ag-primed female mice, generated few antibody forming cells (AFC) following interaction with activated CD4+T cells. In addition, B cells from male BXSB mice, unlike B cells from female BXSB mice, failed to upregulate MHC class II molecules following interaction with activated CD4+ T cells. Subsequent experiments revealed that the inability of the B cells from the male mice to upregulate MHC class II molecules in response to T cell-mediated activation resided primarily in the population of large B cells. Large B cells from male BXSB mice were also defective in their ability to proliferate following stimulation with activated CD4+ T cells. Taken together, these findings demonstrated that similar to B cells in lupus patients, large B cells from male BXSB mice could function in a hyporesponsive manner, and that this hyporesponsiveness related to the inability of the B cells to interact in a positive manner with CD4+T cells.
Blossom
S J
SJ
Department of Microbiology and Immunology, University of Arkansas for Medical Sciences, Little Rock, 72205, USA.
Gilbert
K M
KM
D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000378:metabolism; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D012737:Sex Factors; D015398:Signal Transduction; D015854:Up-Regulation
D019013:CD40 Antigens; D000949:Histocompatibility Antigens Class II; D023201:CD40 Ligand