Lymphocyte memory and affinity selection

Abstract

The persistence of antigen-specific immune memory appears to require the presence of antigen--suggesting that memory may be due to restimulation of "memory" lymphocytes by persisting antigen. Persistence of antigen, in a form capable of stimulating B cell proliferation, on long-lived, follicular dendritic cells of lymphoid tissue is well documented. Existence of an analogous mechanism for T cell memory maintenance is controversial but can not be ruled out. Here we examine the consequences of immune memory maintenance by antigen-specific lymphocyte restimulation, and estimate the duration of memory as a function of model parameters. We show that the competition for restimulation among memory cell populations results in the selection of the clone having the highest overall affinity for the retained antigen. Thus affinity selection, an important attribute of immunity, is a constitutive property of memory maintenance by antigen-specific restimulation. In the case of B cells, affinity selection is predicted to continue to increase antibody affinity even after somatic mutation stops, and thus may be an important component of affinity maturation. Finally, we discuss several other hypotheses proposed to explain immune memory, including T cell stimulation by cross-reactive antigens.