title: Polyclonal B cell activation by a B cell differentiation factor, B151-TRF2. III. B151-TRF2 as a B cell differentiation factor closely associated with autoimmune disease.
abstract: We demonstrated previously that B151K12 T cell hybridoma produces two distinct B cell differentiation factors, B151-TRF1 and B151-TRF2, capable of inducing differentiation of antigen-activated and unstimulated B cells into antibody-forming cells, respectively. In the present study we investigated the pathophysiologic relation of these factors with factors obtained from MRL/MP-lpr/lpr(MRL/lpr) mice and (C57BL/6 X DBA/2)F1 (BDF1) mice undergoing chronic graft-vs-host reaction (GVHR), representing a murine model of systemic lupus erythematosus with polyclonal B cell activation associated with the T cell hyperfunction. The functional and biochemical analyses revealed that B151-TRF2-like, but not B151-TRF1-like, activity was found in culture fluid supernatant (CFS) of lymphoid cells from MRL/lpr mice with lymphoproliferative syndrome. On the other hand, both B151-TRF1- and B151-TRF2-like activities were detected in CFS prepared from spleen cells of BDF1 mice undergoing chronic GVHR by the inoculation of parental DBA/2 spleen cells. Interestingly, spleen cells of BDF1 mice transferred with DBA/2 thymocytes preferentially elaborated B151-TRF1-like factor. Because BDF1 mice transferred with DBA/2 spleen cells but not with DBA/2 thymocytes developed a SLE-like syndrome exemplified by the appearance of Coombs' antibody and proteinuria, it seemed likely that production of B151-TRF2-like factor was closely associated with the onset of autoimmune disease. In fact, B151-CFS containing B151-TRF2 but not B151-TRF1 activity could induce a striking autoantibody production both in vivo and in vitro as detected by PFC responses of normal mice to bromelain-treated mouse red blood cells (BrMRBC). Moreover, it was demonstrated that in vitro anti-BrMRBC PFC responses induced by semipurified B151-TRF2 was markedly inhibited by addition of relevant anti-Ia antibody to the culture. Thus, the present study demonstrates that B151-TRF2 represents one of the B cell differentiation factors responsible for polyclonal B cell activation leading to autoantibody production.
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000209:etiology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D006087:Graft vs Host Reaction; D006133:Growth Substances / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology*; D006462:Hemolytic Plaque Technique; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D015847:Interleukin-4; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects*; D008222:Lymphokines / Q000032:analysis / Q000096:biosynthesis / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D001323:Autoantibodies; D006133:Growth Substances; D000949:Histocompatibility Antigens Class II; D008222:Lymphokines; D015847:Interleukin-4