B-cell-tropic interleukins in murine systemic lupus erythematosus (SLE) 1.
Functional in vitro studies of B cells from 3 murine strains which develop severe early onset SLE-like disease with marked polyclonal B cell hyperactivity lead to the following conclusions: 1.) B cell proliferation and differentiation in lupus mice remains dependent on accessory signals of either macrophage or T cell origin; 2.) B cells from BXSB, NZB/W and MRL/1 mice appear to require the same number and type of signals as normal B cells to undergo polyclonal or antigen-directed responses. B cells of BXSB and NZB/W, but not MRL/1, origin differ from normal B cells by their higher sensitivity (or degree of response) to the signals they receive; 3.) Proliferating T cells in enlarged nodes and spleens of older MRL/1 mice, in the absence of mitogens, secrete in vitro abnormally high levels of a factor (L-BCDF) inducing terminal differentiation of activated B cells to Ig secreting cells. Based on these findings, murine SLE can be divided into 2 main types which may, nevertheless, share some characteristics: Type 1 murine SLE, characterized by primary B cell hyperresponsiveness to activating signals and lymphokines promoting B cell growth and differentiation (NZ and BXSB strains); and, Type 2 murine SLE, characterized by T helper cell hyperactivity and overproduction by proliferating T cells of one or more B cell differentiation factors (MRL/1 strain). In both types of murine SLE, abnormal responses to accessory signals or overproduction of differentiation-inducing signals ultimately leads to polyclonal and auto-antigen specific B cell expansion, hypergammaglobulinemia and auto-antibody production, and Ig gene rearrangement (IgM to IgG switching), resulting in the production of pathogenic IgG type auto-antibodies and disease.
D000818:Animals; D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002455:Cell Division; D004195:Disease Models, Animal; D005260:Female; D006133:Growth Substances / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D015847:Interleukin-4; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology* / Q000662:veterinary; D008213:Lymphocyte Activation; D008211:Lymphocyte Cooperation; D008222:Lymphokines / Q000276:immunology*; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000276:immunology; D012376:Rodent Diseases / Q000235:genetics / Q000276:immunology
D000944:Antigens, Differentiation, B-Lymphocyte; D000954:Antigens, Surface; D006133:Growth Substances; D007074:Immunoglobulin G; D008222:Lymphokines; D015847:Interleukin-4