title: Resting B cells from autoimmune lupus-prone New Zealand Black and (New Zealand Black x New Zealand White)F1 mice are hyper-responsive to T cell-derived stimuli.
abstract: To determine whether B cells from New Zealand Black (NZB) and (New Zealand Black x New Zealand White)F1 (NZB/W) mice possess intrinsic defects that lead to altered immune responsiveness, we purified resting B cells from these mice and compared their surface phenotype and function with those of resting B cells isolated from BALB/c and DBA/2 nonautoimmune mouse strains. Flow cytometric analysis of freshly isolated resting B cells revealed that NZB and NZB/W resting B cells are conventional B2-type cells similar to their nonautoimmune counterparts. Despite this, resting B cells from young NZB and NZB/W mice express lower levels of CD23 on their surface and aberrant levels of intracellular IgM. Upon stimulation, resting B cells from young NZB and NZB/W mice demonstrate increased proliferation, IgM secretion, or enhanced expression of costimulatory molecules in response to a variety of different T cell-derived stimuli, including cytokines and signals generated through CD40. Therefore, B cell hyper-responsiveness to T cell stimuli is immunodominant or codominant in NZB/W mice. Taken together, our results suggest that intrinsic B cell hyper-responsiveness may play a role in the pathogenesis of autoimmune disease in NZB and NZB/W mice. The increased clonal expansion of these B cells together with increased Ig production and enhanced costimulatory capacity serve to amplify the immune response. In the context of normal but incomplete T cell tolerance, B cell hyperresponsiveness to the limited signals provided by partially tolerant T cells may be sufficient to yield an autoantibody response.
authors.affiliation: The Arthritis Center, The Toronto Hospital, University of Toronto, Ontario, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Jongstra-Bilen
authors.forename: B
authors.initials: B
authors.lastname: Vukusic
authors.forename: K
authors.initials: K
authors.lastname: Boras
authors.forename: J E
authors.initials: JE
authors.lastname: Wither
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000276:immunology; D003433:Crosses, Genetic; D016207:Cytokines / Q000494:pharmacology; D004198:Disease Susceptibility; D005260:Female; D007075:Immunoglobulin M / Q000096:biosynthesis; D016130:Immunophenotyping; D007399:Interphase / Q000276:immunology*; D007424:Intracellular Fluid / Q000276:immunology / Q000378:metabolism; D008181:Lupus Nephritis / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000235:genetics; D008211:Lymphocyte Cooperation; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008814:Mice, Inbred NZB / Q000235:genetics / Q000276:immunology*; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D019013:CD40 Antigens; D016207:Cytokines; D007075:Immunoglobulin M