CD86 regulates IgG1 production via a CD19-dependent mechanism.
CD86 signals directly in a B cell to activate PI3K and increase the rate of IgG(1) production, without affecting germline transcription. However, the mechanism by which CD86 activates PI3K in a B cell and the relevance of CD86 stimulation in vivo remains unknown. We show that the addition of CD28/Ig to CD40 ligand/IL-4-activated wild-type, but not CD86- or CD19-deficient, B cells increased the level of phosphorylation for Lyn and CD19, as well as the amount of Lyn, Vav, and PI3K that immunoprecipitated with CD19. Adoptive transfer of CD86-deficient B cells and wild-type CD4(+) T cells into RAG2-deficient mice and immunization with trinitrophenylated keyhole limpet hemocyanin resulted in an IL-4 and germline IgG(1) response equivalent to control mice, but a decrease in serum IgG(1). Thus, our findings suggest that CD86 plays a key role in regulating the level of IgG(1) produced in vitro and in vivo, and that Lyn and CD19 may be the signaling intermediates activated by CD86 proximal to PI3K.
Kin
Nicholas W
NW
Department of Molecular Virology, Immunology, and Medical Genetics, The Ohio State University, Columbus, OH 43210.
Sanders
Virginia M
VM
D019264:Adoptive Transfer; D000818:Animals; D018941:Antigens, CD19 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000637:transplantation; D051940:B7-2 Antigen / Q000235:genetics / Q000502:physiology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D015536:Down-Regulation / Q000235:genetics / Q000276:immunology; D005260:Female; D007074:Immunoglobulin G / Q000096:biosynthesis* / Q000235:genetics; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050813:Octamer Transcription Factor-2 / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000172:deficiency / Q000235:genetics
D018941:Antigens, CD19; D051940:B7-2 Antigen; D007074:Immunoglobulin G; D050813:Octamer Transcription Factor-2; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4