Profile Ryan Heiser

Summary of Research:
A basic problem in immunoregulation is how CD4+ T cells handle neo antigens in the B cell receptor (BCR) that arise from somatically generated antibody diversity, are presented in MHC II, and are amplified by B cell clonal expansion during immune responses. Some of this diversity in CDR3 predates B cell activation, while the rest is created via somatic hypermutation. BCR neo antigens can provide an avenue of T cell help that is potentially dangerous, because it is not restricted to B cells engaging foreign immunogen. To determine whether this avenue of help is normally prevented, we developed an adoptive transfer model based on a pair of transgenic mice, one of which expresses a κ light chain containing a defined T cell epitope, and the other of which expresses a transgenic αβTCR capable of engaging this epitope when presented in MHC II. These transgenic B and T cells were transferred into κ-deficient recipient mice that were immunized with a goat anti-mouse κ antibody to model a scenario where B cells involved in an immune response to a foreign antigen interact with CD4+ T cells specific for somatically generated BCR epitopes. Our data indicate that BCR-specific T cell help aborts ongoing germinal center reactions in favor of a short-lived plasmablast response within the red pulp and T cell areas. Furthermore, secondary immune responses are absent in these animals. This supports the idea that, under physiological conditions, BCR-directed CD4+ T cells inhibit the development of memory B cells.