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

Tulane University Of Louisiana, New Orleans LA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Memory B cells are generated in germinal centers and contribute to humoral immunity by rapidly differentiating into plasma cells. Recent report on HIV pathogenesis suggests that the virus associated premature exhaustion of tissue-like memory B cells may lead to poor antibody responses in HIV infected individuals. Here we have demonstrated the 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 have also studied the role of single positive CD27+ B cells isolated from peripheral blood compared to their 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 3 days of stimulation. Furthermore, their immunoglobulin production is not dependent on T cell help suggestive of memory B cells. We have also observed an increased proliferation of CD21+CD27+ B cells in the tonsil followed by spleen, jejunum lamina propria, lymph node and peripheral blood from normal uninfected rhesus macaques after single BrdU inoculation. Following SIV infection the proliferation of CD21+CD27+ memory B cells dramatically decreased in all the tissues as compared to normal uninfected macaques. A significant reduction of CD21+CD27+ memory B cells was evident in tonsil (p0.004). These data suggest that SIV infection may contribute defective antibody response by inhibiting memory B cell proliferation in tissues.