Molecular analysis of clonal stability and longevity in B cell memory.

We used the antiphosphocholine response induced by Proteus morganii and an adoptive transfer protocol to study the contribution of individual clones to B cell memory. Spleen cells from donor mice immunized with P. morganii were injected into irradiated hosts. These recipients were then immunized and their spleen cells fused 12 to 14 wk thereafter. The sequences of hybridoma VH and VL were obtained and DNA rearrangements at both V region loci were studied to ascertain clonal relationships. In all three adoptive transfer experiments, each mouse of a pair receiving cells from the same donor contained hybridomas which were clonally related to each other. In two of these experiments paired recipients possessed cells that had identically mutated V genes. These results lead us to conclude that once a B cell clone(s) dominates a response, progeny of that clone form the memory cell population for many months. Moreover, stability appears to be generated in some memory B cells through inactivation of the hypermutation mechanism.