B-1 cells in systemic autoimmune responses: IgM+, Fc epsilon Rdull B cells are lost during chronic graft-versus-host disease but not in murine AIDS or collagen-induced arthritis.
The potential role of B-1 cells (i.e. the CD5+ B cell and "sister" B cell subsets) in autoimmunity is controversial. CD5+ B cells have been shown to secrete antibodies of similar specificity as those found in many systemic autoimmune diseases; in addition, increases in CD5+ B cell frequency have been reported in patients suffering from rheumatoid arthritis, Sjögren's syndrome, myasthenia gravis, insulin-dependent diabetes mellitus and Hashimoto's thyroiditis. Whether these increases are due to expansion of B-1 lineage cells in the human or due to activation-induced expression of CD5 by conventional B cells is unclear. In the present study, we used three murine models of systemic autoimmunity: murine acquired immunodeficiency syndrome (MAIDS), chronic graft-versus-host disease (cGvHD), and collagen-induced arthritis (CIA) to determine whether increases in B-1 cell frequency are universally seen in models of autoimmunity which are mechanistically distinct. In contrast to the aforementioned human systemic autoimmune diseases which exhibit an increase in CD5+ B cell frequency, the percentage of CD5+ B cells declined in all three murine models of systemic autoimmune disease. Even though there was a decrease in the frequency of CD5+ B cells there was no change in the actual number of CD5+ B cells. Thus, the apparent decline in CD5+ B cell frequency was due to increases in either T cells, conventional Fc epsilon R+ B cells, or both. The only actual decline in a B cell subset was the loss of IgM+, Fc epsilon Rdull cells in both the spleen and peritoneal cavity of mice undergoing a chronic graft-versus-host reaction. Therefore, our data suggests that expansion of the B-1 subset does not occur as a general feature of murine systemic autoimmune disease. These observations, consistent with previous studies of Ig gene usage in autoreactive antibodies, support the view that expansion and differentiation of the CD5+ B cell subset is not a central event leading to autoantibody production.
Iciek
L A
LA
Department of Microbiology, Michigan State University, East Lansing 48824.
Waldschmidt
T J
TJ
Griffiths
M M
MM
Brooks
K H
KH
D000818:Animals; D015703:Antigens, CD / Q000276:immunology*; D001169:Arthritis, Experimental / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens; D002908:Chronic Disease; D003094:Collagen / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006086:Graft vs Host Disease / Q000276:immunology; D007132:Immunoglobulin Isotypes / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D016183:Murine Acquired Immunodeficiency Syndrome / Q000276:immunology; D017455:Receptors, IgE / Q000276:immunology; D013154:Spleen / Q000166:cytology
D015703:Antigens, CD; D001323:Autoantibodies; D018956:CD5 Antigens; D007132:Immunoglobulin Isotypes; D017455:Receptors, IgE; D003094:Collagen