We specifically study the control of antigen receptor gene assembly, differentiation and function of memory T and B cells, and the role of natural IgM in immunity and autoimmunity. . . Although recombination is mediated through a common recombinase and conserved recombination signals that flank the gene segments, the process is highly regulated in vivo. Finally, only one of the two alleles is functionally recombined and expressed, a process referred to as allelic exclusion. Evidence suggests that different controls are mediated by modulating chromatin structures of gene segments and therefore their accessibility to the common recombinase. We have found that localized promoter elements target specific gene segments for rearrangement.
Immunological memory is a central feature of adaptive immunity and is the basis of vaccination.
However, little is known about the differentiation, reactivation, and function of memory T cells because of a lack of identifiable markers and their low abundance. We have developed an adoptive transfer protocol by which a substantial number of memory T cells can be generated. When freshly isolated from mice memory cells killed target cells without having to be restimulated. These findings suggest that, unlike naive T cells, CD8 memory T cells are intrinsically progammed to rapidly express their effector functions in vivo without having to undergo clonal expansion and differentiation. We are investigating the signals that lead to the chromatin changes during memory T cell differentiation.