IMPORTANCE OF ANTIGEN SPECIFIC IGA RESPONSES IN CONTROLLING SIV/SHIV INFECTION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Memory B cells are generated in germinal centers and contribute to humoral immunity by rapidly differentiating into plasma cells. A recent report on HIV pathogenesis suggests that disease progression is associated with premature exhaustion of memory B cells that may lead to poor antibody responses in HIV infected individuals. Here we demonstrate expression of CD21 and CD27 molecules on B cells isolated from different tissues as well as their rate of proliferation in both normal healthy uninfected and SIVMAC251 infected rhesus macaques. We also studied the role of single positive CD27+ B cells isolated from peripheral blood compared to double positive (CD21+CD27+) B cell counterparts in inducing immunoglobulin production after in vitro mitogen stimulation. Our findings demonstrate that CD27 expression on B cells varies in different tissues and that double positive CD21+CD27+ B cells are capable of producing increased IgG compared to single positive CD27+ B cells after 6 days of stimulation. Furthermore, their immunoglobulin production is not dependent on T cell help, suggestive of memory B cells. We also observed increased proliferation of CD21+CD27+ B cells in the tonsil followed by spleen, lamina propria of the jejunum, lymph node and peripheral blood from normal uninfected rhesus macaques after a single BrdU inoculation. Following SIV infection a significant reduction of CD21+CD27+ memory B cells was evident in tonsil (p0.05) compared to normal uninfected macaques whereas, the proliferation of CD21+CD27+ memory B cells dramatically increased in lymph node and spleen tissues. These data demonstrate functional qualities (activation) of nonhuman primate B cell subsets and suggest that SIV infection may induce defective responses in specific tissues, by inhibiting memory B cell proliferation in tissues.