In vitro induction of immunoglobulin A (IgA)- and IgM-secreting plasma blasts by cholera toxin depends on T-cell help and is mediated by CD154 up-regulation and inhibition of gamma interferon synthesis.
Cholera toxin (CT) and the type II heat-labile enterotoxins (LT-IIa and LT-IIb) are potent immunological adjuvants which are hypothesized to enhance the production of antibody (Ab)-secreting cells, although their mechanisms of action are not fully understood. The treatment of splenic cells with concanavalin A (ConA) plus CT enhanced the production of immunoglobulin A (IgA) and IgM by dividing cells that expressed high levels of major histocompatibility complex class II (MHC-II), CD19, and CD138 and low levels of B220 a phenotype characteristic of plasma blasts. LT-IIa or LT-IIb moderately enhanced IgA and IgM production without enhancing plasma blast differentiation. CT up-regulated CD25, CD69, CD80, CD86, and MHC-II in isolated B cells but failed to induce proliferation or differentiation. The treatment of unfractionated splenic cells with ConA plus CT induced B-cell proliferation and differentiation, but the elimination of CD4(+) T cells inhibited this effect. CT treatment of ConA-activated CD4(+) T cells up-regulated CD134 and CD154, whereas the blockage of CD40-CD154 interactions inhibited the induction of plasma blasts and Ig synthesis. The treatment of unfractionated splenic cells with CT, LT-IIa, or LT-IIb enhanced the production of interleukin-6 (IL-6) and IL-10, whereas the production of gamma interferon was inhibited in both CD4(+) and CD8(+) T cells mostly by CT. Thus, major regulatory effects of CT on lymphocytes are likely exerted early during the induction of immune responses when B and T cells initially encounter antigen. Neither LT-IIa or LT-IIb had these effects, indicating that type II enterotoxins augment Ab responses by other mechanisms.
Arce
Sergio
S
The Department of Microbiology and Immunology, School of Medicine and Biomedical Sciences, University at Buffalo, SUNY, 138 Farber Hall, 3435 Main St., Buffalo, NY 14214, USA. arce@buffalo.edu
Nawar
Hesham F
HF
Muehlinghaus
Gwendolin
G
Russell
Michael W
MW
Connell
Terry D
TD
D000818:Animals; D023201:CD40 Ligand / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000276:immunology*; D007070:Immunoglobulin A / Q000096:biosynthesis*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010950:Plasma Cells / Q000276:immunology* / Q000378:metabolism; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
D007070:Immunoglobulin A; D007075:Immunoglobulin M; D023201:CD40 Ligand; D007371:Interferon-gamma; D002772:Cholera Toxin