Hongli Hu, PhD, Postdoctoral Fellow Boston Children's Hospital One way the immune system protects us from diverse pathogens is by generating billions of B lymphocytes, each armed with a different form of pathogen-recognizing B cell receptor (BCR). Together the billions of different BCRs on different B cells recognize almost any encountered pathogen. When a B cell recognizes a particular pathogen, it fights it by secreting its BCR as an antibody. Antibody subunits have a pathogen-recognizing sequence termed variable regions that are different in each BCR. The number of different BCRs in our body is far greater than could be encoded by our genes. Developing B cells accomplish this genetic feat by cutting and pasting genetic cassettes together into sequences that encode variable regions by a process termed V(D)J recombination. As these genetic cassettes are spread across long chromosomal distances, the mechanism by which they find each other during V(D)J recombination was a mystery. It was recently discovered that developing B cells harness a genetic process termed chromatin loop extrusion to reel widely separated variable region cassette-containing chromosomal regions past each other at a genetic site where they are cut and pasted. Projects and Grants Role of cohesin mediated loop extrusion in antibody repertoire development Boston Children’s Hospital | All Cancers | 2022 | Frederick W. Alt, Ph.D.
