Our B cells can create a nearly limitless diversity of antibodies to target threats, including virus-infected cells as well as cancer cells. This is due to B cells’ ability to rearrange—mix and match, so to speak—different portions of the antibody-encoding genes via a process known as V(D)J recombination. Unfortunately, of these essentially randomly generated antibodies may target molecules on our healthy cells and cause auto-immune reactions. While a process known as allelic exclusion seeks to minimize this, the mechanisms behind it aren’t fully known.
Recently, Dr. Dai identified a potentially new component of allelic exclusion mechanisms that works independently of previously discovered mechanisms. Now, with the state of the art technologies and experimental models, Dr. Dai aims to further explore this component in order to better define how it fits into the other mechanisms involved in allelic exclusion. The insights he uncovers could then help improve our understanding both of normal antibody repertoire development and mechanisms by which defects in allelic exclusion may contribute to autoimmunity and B cell cancers.
Projects and Grants
Elucidation of feedback and other mechanisms of IgH allelic exclusion for production of therapeutic bispecific antibodies in vivo
Boston Children’s Hospital | All Cancers | 2019 | Frederick W. Alt, Ph.D.
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