Towards Identification of Memory B Cells in Human Tonsils

Abstract

Unravelling the mechanisms underlying the generation of B cell memory is an important issue for improvement of the actual modes of vaccination and for the design of new vaccines. However, to this date, our knowledge of the phenotype and properties of memory B cells in humans is still rudimentary, possibly because of the difficulty to assess memory on a functional basis in the human system. It is now widely agreed that memory B cells are generated through a process of positive selection occurring within the germinal centers of secondary follicles. Based on the generally accepted notion that memory B cells express classes of antibodies other than IgM and IgD on their surface, we made the assumption that memory B cells should be searched for in the B cell population lacking expression of surface IgD. Thus, we examined the distribution of several surface markers on purified IgD- B cells isolated from tonsils and found that expression of CD10, CD38 and CD44 distinguished two major B cell subsets among the IgD- B cell compartment. We subsequently separated the two B cell types and performed further phenotypical analysis and functional studies which showed that one of these IgD- B cell populations displays most of the features commonly ascribed to memory B cells. In the present paper we review the experimental data which support this hypothesis and propose a putative scheme of the memory B cell differentiation pathway.