Memory B cells at successive stages of differentiation: expression of surface IgD and capacity for self renewal.

In recent studies, we have characterized two memory B cell populations capable of giving rise to IgG antibody-producing cells in adoptive recipients. One population carries surface IgD gives rise to predominantly low-affinity antibody responses; the other lacks detectable surface IgD and gives rise to predominatly high-affinity responses. These memory populations often coexist in individual donors for long periods of time; however, in strongly stimulated donors, the IgD+ population is lost after several weeks, and nearly all detectable B cell memory is IgD- thereafter. In this publication, we show that the IgD+ and IgD- memory populations represent B cells at two successive stages of antigen-dependent differentiation. We used the fluorescence-activated cell sorter (FACS) in a double isolation and transfer protocol to show directly that FACS-isolated IgD+ memory cells transferred to adoptive recipients give rise both to IgG antibody-producing cells and to an expanded memory population that is predominantly IgD-. We also show that FACS-isolated IgD- memory populations from the original donor "self-renew" (i.e. give rise to more IgD- memory) in adoptive recipients and that these events require supplementation of the isolated memory cells with carrier-primed T cells and antigen. In discussing these findings, we integrate our data with previous evidence on the expression of surface IgG on memory B cells to create an updated view of surface Ig expression during memory development. We also consider these findings in the light of our recent suggestion that the loss of IgD receptors facilitates affinity maturation in the more mature (IgD-) memory population.