The evolution of B-cell clones.

This chapter identifies three forms of B-cell memory: (a) B blasts which characterize the established stage of the follicular response to TD antigens, (b) recirculating memory B cells, and (c) non-recirculating memory B cells of the marginal zones of the spleen and equivalent areas of other secondary lymphoid organs. The follicular B blasts show sustained proliferation driven by small amounts of antigen bound to FDCs. The probable relationships between these cells is summarized diagrammatically in Fig. 4. It is probable that follicular B blasts generate both the recirculating and marginal zone memory cells. The chapter by Gray and Leanderson in this volume cites data which indicate that the recirculating memory pool is not sustained for more than a few weeks in the absence of antigen. Data leading to the same conclusion for marginal zone memory B cells is set out in Sect. 5.1 of this chapter. Marginal zone memory B cells do not appear to move spontaneously to follicles for periodic renewal. They will only leave the marginal zone if a fresh supply of antigen reaches them in that site. Recirculating B cells are able to respond to antigen already held on FDCs. It is not known if they are able to displace B blasts of equivalent affinity for antigen which already occupy antigen-holding sites on FDCs. This could be a mechanism by which B blasts with high antigen affinity produced in one follicle could displace blasts of lower affinity in other follicles. Little is known of the factors which regulate the numbers of marginal zone and recirculating follicular memory B cells. In responses to hapten-protein conjugates, hapten-binding cells may approach 10% of marginal zone B cells but comprise well under 1% of recirculating follicular cells. The numbers of these memory cells do not increase if the recirculating pool of lymphocytes is depleted, indicating that the factors which regulate the number of memory B cells are independent of those which regulate the total size of the recirculating B-cell pool. A depleted peripheral B-cell pool can only be fully reconstituted by recruitment of newly produced virgin B cells. Data cited in Sect. 5.2 support the concept that this recruitment is at least partially independent of antigen-driven B-cell proliferation. Consequently, substantial proportions of the peripheral B-cell pools are likely to be either virgin cells or cells which have been recruited by antigen or anti-idiotype without entering cell cycle.(ABSTRACT TRUNCATED AT 400 WORDS)