title: Murine B1 B cells require IL-5 for optimal T cell-dependent activation.
abstract: T helper cell-driven activation of murine B cells has been shown to depend upon CD40-CD40 ligand (CD40L) interactions and a defined set of cytokines. These observations are primarily based on the use of conventional B cells obtained from the spleen. Therefore, it is presently unclear whether all mature B cell subsets found in the mouse have an equal dependence upon CD40-CD40L interactions and use the same T cell-derived cytokines. The present study tested the response of splenic follicular and marginal zone as well as peritoneal B2 and B1 B cells to Th cell stimulation. Splenic and peritoneal B cell subsets were sort purified based on CD23 expression, and cultured with rCD40L and cytokines or Th2 cells. The results demonstrate that follicular, marginal zone, and peritoneal B2 B cells require CD40-CD40L interactions and preferentially use IL-4 for optimal proliferation, differentiation, and isotype switching. In contrast, peritoneal B1 B cells use IL-5 in conjunction with CD40-CD40L interactions for maximal Th cell-dependent responses. Furthermore, B1 B cells are capable of proliferating, differentiating, and isotype switching in the absence of CD40-CD40L interactions. B1 B cells are able to respond to Th2 clones in the presence of anti-CD40L mAb as well as to Th2 clones derived from CD40L(-/-) mice. The CD40-CD40L-independent response of B1 B cells is attributable to the presence of both IL-4 and IL-5, and may explain the residual Ab response to T cell-dependent Ags in CD40L- or CD40-deficient mice, and in X-linked hyper-IgM (X-HIM) patients.
authors.affiliation: Department of Pathology and Immunology Graduate Program, University of Iowa College of Medicine, Iowa City, IA 52242, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Erickson
authors.forename: T M
authors.initials: TM
authors.lastname: Foy
authors.forename: T J
authors.initials: TJ
authors.lastname: Waldschmidt
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001202:Ascitic Fluid / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D019013:CD40 Antigens / Q000096:biosynthesis; D023201:CD40 Ligand / Q000235:genetics / Q000276:immunology / Q000494:pharmacology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D002999:Clone Cells; D018920:Coculture Techniques; D005260:Female; D007106:Immune Sera / Q000494:pharmacology; D017578:Immunoglobulin Class Switching / Q000276:immunology; D007136:Immunoglobulins / Q000096:biosynthesis; D015847:Interleukin-4 / Q000494:pharmacology; D015848:Interleukin-5 / Q000276:immunology / Q000494:pharmacology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D011994:Recombinant Proteins / Q000494:pharmacology; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D019013:CD40 Antigens; D007106:Immune Sera; D007136:Immunoglobulins; D015848:Interleukin-5; D011994:Recombinant Proteins; D023201:CD40 Ligand; D015847:Interleukin-4