Reduced T cell expansion by a superantigen as a result of impaired B cell development in mice deficient for the p85alpha regulatory subunit of PI3K.
PI3K plays crucial roles in the immune system. Mice deficient for p85alpha, 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 Vbeta3(+)CD4(+) T cells, whereas the same treatment induced T cell expansion in p85alpha-deficient mice but to a much lesser extent than in normal mice. However, mixed bone marrow chimera mice, which have normal and p85alpha-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 p85alpha-deficient mice into Rag2-deficient mice, followed by SEA stimulation, p85alpha-deficient T cells revealed much higher proliferative capacity in the presence of normal B cells than did normal T cells with p85alpha-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, p85alpha-deficient B cells had a low level of MHC class II expression. Collectively, these data suggested that the PI3K p85alpha 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.
Arimura
Yutaka
Y
Department of Microbiology, Tokyo Women's Medical University School of Medicine, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan. arimura@research.twmu.ac.jp
Ezaki
Taichi
T
Koyanagi
Madoka
M
Uchiyama
Takehiko
T
Koyasu
Shigeo
S
Yagi
Junji
J
D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology* / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology* / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004768:Enterotoxins / Q000494:pharmacology; D005260:Female; D015918:Infusion Pumps, Implantable; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019869:Phosphatidylinositol 3-Kinases / Q000172:deficiency* / Q000378:metabolism; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D018089:Superantigens / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
D004768:Enterotoxins; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D051020:bcl-X Protein; C026066:enterotoxin A, Staphylococcal; D019869:Phosphatidylinositol 3-Kinases