B2 but not B1 cells can contribute to CD4(+) T-cell-mediated clearance of rotavirus in SCID mice

Studies utilizing various immunodeficient mouse models of rotavirus (RV) infection demonstrated significant roles of RV-specific secretory immunoglobulin A (IgA), CD4(+) T cells, and CD8(+) T cells in the clearance of RV and protection from secondary infection. Secretion of small but detectable amounts of IgA in RV-infected (YP T-cell receptor knockout mice (11) and distinctive anatomical localization and physiology of BI cells suggested that BL cells might be capable of producing RV-specific intestinal IgA in a T-cell-independent fashion and, therefore, be responsible for ablation of RV shedding, We investigated the role of B1 cells in the resolution of primary RV infection using a SCID mouse model. We found that the adoptive transfer of unseparated peritoneal exudate cells ablates RV shedding and Leads to the production of high levels of RV-specific intestinal IgA, In contrast, purified B1 cells do not ablate RV shedding and do not induce a T-cell-independent or T-cell-dependent, RV-specific IgA response but do secrete large amounts of polyclonal (total) intestinal IgA, Cotransfer of mixtures of purified B1 cells and Iii-cell-depleted peritoneal exudate cells differing in IgA allotypic markers also demonstrated that B2 cells (BI-cell-depleted peritoneal exudate cells) and not B1 cells produced RV-specific IgA, To our knowledge, this is the first observation that B1 cells are unable to cooperate with CD4(+) T cells and produce virus-specific intestinal IgA antibody. We also observed that transferred CD4(+) T cells alone are capable of resolving RV shedding, although no IgA is secreted. These data suggest that RV-specific IgA may not be obligatory for RV clearance but may protect from reinfection and that effector CD4(+) T cells alone can mediate the resolution of primary RV infection. Reconstitution of RV-infected SCID mice with B1 cells results in the outgrowth of contaminating, donor CD4(+) T cells that are unable to clear RV, possibly because their oligoclonal specificities may be ineffective against RV antigens.