Activation induced cytidine deaminase is highly expressed on CD99+Faslow Ramos cells; implication in the early centroblast stage (45.8)

Abstract

Abstract Ramos cell line, derived from Burkitt’s lymphoma with centroblastic phenotype, has been chosen as a good model for studying somatic hypermutation. To delineate maturation stages of B cells in germinal center (GC) with an expression pattern of CD99 that has been reported to be down-regulated in GC, we sorted and subcloned the Ramos cells according to the expression patterns of CD99. CD99+ clones lost CD99 expression to become CD99- cells spontaneously. However, the reverse event has not happened in any cases. We observed that CD99+ clones have earlier centroblastic phenotypes than CD99- ones through experiments such as IgM-induced apoptosis and Fas expression. When the CD99+ clones were subcloned based on Fas expression levels, CD99+Faslow clones generated IgM- population in higher frequency than CD99+Fashi and CD99-Fashi did, then we evaluated the expression level of AID and found that CD99+Faslow clones are the cells at the stage where AID level is the highest. This high expression level of AID in the CD99+Faslow clones is pertinent to the Ramos cells sorted directly and also to different Burkitt’s lymphoma cell lines: Daudi, BJAB, and Raji. These results suggest that AID is differentially expressed between CD99+ and CD99- cells, implying CD99 might be a marker to delineate the maturation stages of B cells in GC. Based on this, we hypothesize that CD99+Faslow cells are immature cells and differentiate into CD99-Fashi with an intermediate step which has CD99+Fashi in GC.