Reduced T cell expansion by a superantigen as a result of impaired B cell development in mice deficient for the p85α regulatory subunit of PI3K

PI3K p85α subunit alters the superantigen presentation capacity of B cells and indirectly modulates the magnitude of the T cell response. PI3K plays crucial roles in the immune system. Mice deficient for p85α, a major regulatory subunit of class IA PI3K, show various defects and alterations in B cells, mast cells, macrophages, and DCs, and peripheral T cells are reportedly normal, at least in vitro. In normal mice, long‐term exposure to a SAg, SEA, in vivo induced a high level of the protracted expansion of SEA‐reactive Vβ3+CD4+ T cells, whereas the same treatment induced T cell expansion in p85α‐deficient mice but to a much lesser extent than in normal mice. However, mixed bone marrow chimera mice, which have normal and p85α‐deficient T and B cells, demonstrated equal responses of both T cells following stimulation with a SEA pump. In reciprocal cotransfer experiments of T and B cells from normal and p85α‐deficient mice into Rag2‐deficient mice, followed by SEA stimulation, p85α‐deficient T cells revealed much higher proliferative capacity in the presence of normal B cells than did normal T cells with p85α‐deficient B cells. Histologically, a marked B cell reduction was observed in the follicles and MZ of the spleen, and DCs accumulated in the MZ. In addition, p85α‐deficient B cells had a low level of MHC class II expression. Collectively, these data suggested that the PI3K p85α subunit alters the SAg presentation capacity of B cells and indirectly modulates the magnitude of the T cell response, which may affect the protection against SEA‐containing bacteria.