Proliferation of Ly-1 B cells in autoimmune NZB and (NZB x NZW)F1 mice.
Spontaneous autoimmune disease in NZB and (NZB x NZW)F1 (B/W) mice is associated with a spectrum of lymphoproliferative abnormalities, but the relationship between autoimmunity and lymphoproliferation is poorly understood. Lymphomas occur commonly in NZB mice, but they appear to be rare in B/W mice, perhaps because B/W mice die of murine lupus before the lymphomas are evident. We recently reported that autoimmune disease in B/W mice could be reversed by weekly treatment with monoclonal antibodies to the L3T4 antigen on "helper/inducer" T cells. This has enabled us to examine the evolution of lymphoproliferation in B/W mice that survive beyond the usual life span, both in long-term survivors of treatment with anti-L3T4 and in the occasional B/W mouse that spontaneously survives beyond 1 year of age. We find that all of these mice develop marked proliferation of a distinct subpopulation of B cells that express the Ly-1 antigen in low density. These Ly-1+ B cells account for a 2-10-fold increase in the number of splenic, lymph node and peripheral blood lymphocytes. The Ly-1 B cells in individual mice are restricted in their expression of immunoglobulin light chains, suggesting a clonal origin. NZB mice. develop similar proliferation of Ly-1 B cells, suggesting that this is due to underlying genetic and/or viral factors in NZB and B/W mice, and that it is not the result of treatment with anti-L3T4. Although recent studies have implicated Ly-1 B cells in the production of autoantibodies, proliferation of Ly-1 B cells in B/W mice was not associated with production of anti-DNA antibodies or with any paraprotein.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000627:therapeutic use; D000918:Antibody Specificity; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly / Q000276:immunology*; D000954:Antigens, Surface / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality; D001402:B-Lymphocytes / Q000276:immunology*; D004247:DNA / Q000276:immunology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007147:Immunoglobulin Light Chains / Q000235:genetics; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation / Q000187:drug effects; D008212:Lymphocyte Depletion; D051379:Mice; D008814:Mice, Inbred NZB / Q000276:immunology*; D008815:Mice, Inbred Strains; D013154:Spleen / Q000166:cytology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology
D000906:Antibodies; D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D000950:Antigens, Ly; D000954:Antigens, Surface; D007147:Immunoglobulin Light Chains; D004247:DNA