B cell depletion curtails CD4+ T cell memory and reduces protection against disseminating virus infection.
Dynamic interactions between CD4(+) T cells and B cells are needed for humoral immunity and CD4(+) T cell memory. It is not known whether B cells are needed early on to induce the formation of memory precursor cells or are needed later to sustain memory cells. In this study, primary and memory CD4(+) T cells responses were followed in wild-type mice that were depleted of mature B cells by anti-CD20 before or different times after acute lymphocytic choriomeningitis virus infection. The Ab treatment led to a 1000-fold reduction in B cell number that lasted 6 wk. Primary virus-specific CD4(+) Th1 cells were generated in B cell-depleted mice; however, there was a decrease in the CD4(+)Ly6C(lo)Tbet(+) memory precursor population and a corresponding 4-fold reduction in CD4(+) memory cell number. Memory T cells showed impaired cytokine production when they formed without B cells. B cell depletion had no effect on established memory populations. During disseminating virus infection, B cell depletion led to sustained weight loss and functional exhaustion of CD4(+) and CD8(+) T cells, and prevented mice from resolving the infection. Thus, B cells contribute to the establishment and survival of memory CD4(+) T cells post-acute infection and play an essential role in immune protection against disseminating virus infection.
Department of Genetics, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599.
Ichiro
I
Misumi
Jason K
JK
Whitmire
D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000378:metabolism; D018951:Antigens, CD20 / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008212:Lymphocyte Depletion; D008216:Lymphocytic Choriomeningitis / Q000276:immunology* / Q000821:virology; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D000069283:Rituximab; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism
D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000069283:Rituximab