IgG1 production by sIgD+ splenic B cells and peritoneal B-1 cells in response to IL-5 and CD38 ligation.
CD38 ligation on mouse B cells by CS/2, an anti-mouse CD38 mAb, induces proliferation, IL-5 receptor alpha chain expression and tyrosine phosphorylation of Bruton's tyrosine kinase. Furthermore, stimulation of splenic B cells with IL-5 together with CS/2 induces Blimp-1 expression and differentiation into Ig-producing cells. Here we examined the role of IL-5 in IgG1 and IgA production by B cells isolated from the spleen and peritoneal cavity. CD38 recognized by CS/2 was expressed in the follicular mantle B cells surrounding the germinal center, sIgD+ splenic B cells and peritoneal B cells. IL-5 induced IgG1 production in splenic sIgD+ B cells stimulated with CS/2, while it was ineffective to induce IgA production. Among the various cytokines tested, only IL-5 had a synergistic effect on IgG1 production with CS/2. IL-5 could induce the generation of S micro-Sgamma1 reciprocal recombination DNA products in CS/2-stimulated B cells. IL-4 was ineffective to induce either micro-gamma1 switch recombination or IgG1 secretion with CS/2, demonstrating that IL-5 promotes both micro-gamma1 switch recombination and IgG1 secretion in an IL-4-independent manner. The peritoneal B-2 cells exhibited both IgG1 and IgA production in response to IL-5 plus CS/2, while B-1 cells produced IgG1. These results imply that the pattern of differentiation to Ig-producing cells seen with peritoneal B cells is not identical to the pattern seen with splenic B cells and that peritoneal B-2 cells contain precursors of IgA-producing cells responding to IL-5 plus CS/2.
Yasue
T
T
Departments of Immunology and Pathology, Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan.
Baba
M
M
Mori
S
S
Mizoguchi
C
C
Uehara
S
S
Takatsu
K
K
D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000276:immunology* / Q000378:metabolism; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis*; D007134:Immunoglobulin Switch Region; D007142:Immunoglobulin gamma-Chains / Q000096:biosynthesis / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000096:biosynthesis / Q000235:genetics; D015848:Interleukin-5 / Q000276:immunology* / Q000378:metabolism / Q000502:physiology; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009244:NAD+ Nucleosidase / Q000276:immunology* / Q000378:metabolism; D010529:Peritoneal Cavity / Q000166:cytology; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis; D013154:Spleen / Q000166:cytology* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007142:Immunoglobulin gamma-Chains; D007148:Immunoglobulin mu-Chains; D015848:Interleukin-5; D008562:Membrane Glycoproteins; D011947:Receptors, Antigen, B-Cell; D036541:ADP-ribosyl Cyclase; C498155:Cd38 protein, mouse; D009244:NAD+ Nucleosidase; D051997:ADP-ribosyl Cyclase 1