B cell superstimulatory influenza virus activates peritoneal B cells.
We evaluated the potential of B cell "superstimulatory" influenza viruses to activate peritoneal B cells (PBC) from BALB/c mice containing both CD5+ and CD5- "sister" cells. Like conventional B cells, PBCs responded to influenza viruses in a hemagglutinin glycoprotein (HA) subtype-specific manner with proliferation and vigorous Ig synthesis. However, a number of HA subtypes that are highly stimulatory for conventional B cells failed to induce significant responses of PBC. Isotype-determination revealed a high predominance of IgM and only very low production of IgA and IgG. HA-activated CD5+ B cells showed a hyperexpression of various activation markers, including MHC class II, intercellular adhesion molecule 1 (CD54), and B7-1 molecules. In contrast to conventional B cells, where activation by HA is antagonized by phorbol esters (PMA), HA and PMA acted synergistically on PBC, suggesting differential activation requirements of B-2 cells vs PBC in response to HA. Like HA stimulation of B-2 cells, virus-triggered proliferation of PBC was abrogated by a simultaneous treatment with F(ab')2 fragments of anti-Ig Ab and exhibited synergistic effects with LPS stimulation. HA-mediated proliferative responses of PBC, but not of B-2 cells, were positively controlled by various cytokines, including IL-4 and IL-10, and to a lesser extent by IL-6. In conclusion, our data present the first example of a stimulation of peritoneal B cells by a polyclonal-activating virus, findings that call for considering infections with polyclonal B cell-stimulatory viruses as a means of expanding the pool of potentially autoreactive CD5+ B cells.
Rott
O
O
INSERM Unit 283, Cochin Hospital, René Descartes University, Paris, France.
Charreire
J
J
Mignon-Godefroy
K
K
Cash
E
E
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D015703:Antigens, CD / Q000032:analysis; D000956:Antigens, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology; D018956:CD5 Antigens; D002478:Cells, Cultured; D016207:Cytokines / Q000494:pharmacology; D007136:Immunoglobulins / Q000276:immunology; D009980:Influenza A virus / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010529:Peritoneal Cavity / Q000166:cytology*; D010703:Phorbol Esters / Q000494:pharmacology
D000888:Antibodies, Anti-Idiotypic; D015703:Antigens, CD; D000956:Antigens, Viral; D018956:CD5 Antigens; D016207:Cytokines; D007136:Immunoglobulins; D008070:Lipopolysaccharides; D010703:Phorbol Esters