B-CELL SUPERSTIMULATORY INFLUENZA-VIRUS ACTIVATES PERITONEAL B-CELLS

We evaluated the potential of B cell ''superstimulatory'' influenza vi ruses to activate peritoneal B cells (PBC) from BALB/c mice containing both CD5(+) and CD5(-) ''sister'' cells. Like conventional B cells, P BCs 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 con ventional B cells failed to induce significant responses of PBC. Isoty pe-determination revealed a high predominance of IgM and on ly very lo w production of IgA and IgG. HA-activated CD5(+) B cells showed a hype rexpression of various activation markers, including MHC class II, int ercellular adhesion molecule 1 (CD54), and B7-1 molecules. In contrast to conventional B cells, where activation by HA is antagonized by pho rbol 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) fragm ents of anti-Ig Ab and exhibited synergistic effects with LPS stimulat ion. HA-mediated proliferative responses of PBC, but not of B-2 cells, were positively controlled by various cytokines, including IL-4 and I L-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 polyclon al-activating virus, findings that call for considering infections wit h polyclonal B cell-stimulatory viruses as a means of expanding the po ol of potentially autoreactive CD5(+) B cells.