Comparative in vitro analysis of proliferation, Ig secretion, and Ig class switching by murine marginal zone and follicular B cells.
We have previously demonstrated that activation of murine B cells by dextran-conjugated anti-IgD antibodies may serve as a polyclonal, in vitro model system for studying immune responses to T cell-independent type 2 (TI-2) Ag, as exemplified by the bacterial polysaccharides. Because in vivo Ig responses to TI-2 Ag are mediated primarily by B cells resident in the splenic marginal zone, we wished to determine whether this reflected an intrinsic difference in the responsiveness of marginal zone B cells (MZB) compared with follicular B cells (FB) to this class of Ag. In this report we demonstrate that highly purified MZB, isolated by electronic cell sorting, exhibit a lower proliferative response in vitro in response to unconjugated anti-Ig antibody as well as to dextran- or Sepharose-conjugated anti-IgM or anti-IgD antibodies, whereas they proliferate equal to or better than FB when stimulated by other B cell mitogens including LPS, Salmonella typhimurium mitogen, or anti-CD3-activated CD4+ Th2 cell clone. Despite the different proliferative responses of MZB and FB induced by anti-Ig, Ag receptor cross-linkage stimulates comparable increases in intracellular free calcium concentrations in both of these B cell populations. Furthermore, MZB secrete Ig and undergo Ig isotype switching to a comparable degree, relative to FB, in response to both T cell-dependent and T cell-independent stimuli. This suggests that the compartmentalization of TI-2 responses to the splenic marginal zone rather than the follicular zone reflects something other than the intrinsic responsiveness of the B cells from these two sites.
Snapper
C M
CM
Dept. of Pathology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814.
Yamada
H
H
Smoot
D
D
Sneed
R
R
Lees
A
A
Mond
J J
JJ
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology / Q000502:physiology; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D003432:Cross-Linking Reagents; D003911:Dextrans / Q000494:pharmacology; D005260:Female; D007132:Immunoglobulin Isotypes / Q000032:analysis / Q000096:biosynthesis*; D007424:Intracellular Fluid / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008811:Mice, Inbred DBA; D013154:Spleen / Q000166:cytology* / Q000276:immunology
D000945:Antigens, Differentiation, T-Lymphocyte; D003432:Cross-Linking Reagents; D003911:Dextrans; D007132:Immunoglobulin Isotypes; D002118:Calcium