McBride Laboratory

The McBride lab is making fundamental discoveries addressing the biology of B lymphocytes, specialized white blood cells that can differentiate into antibody-producing plasma cells. B cells are critical players in the humoral component of the adaptive immune response. During immune responses, mature B cells diversify immunoglobulin (Ig) genes through somatic hypermutation (SHM) and class-switch DNA recombination (CSR). SHM alters antibody affinity by introducing nucleotide changes in the part of the Ig genes encoding the antigen-binding, variable region of antibodies. B cells that make antibodies with improved antigen affinity are positively selected during the process of affinity maturation. CSR is a region-specific recombination reaction that replaces one antibody-constant region with another, thereby altering antibody effector function while leaving the Ig variable region and its antigen binding specificity intact. These mechanisms lead to the creation of a variety of Ig molecules in an individual, the sum total of which make up the immunoglobulin repertoire for that individual.

Ongoing laboratory research projects are defining the biology of B cells, particularly the molecular processes required for normal antibody immunoglobulin diversification; how B cells in the tumor microenvironment and the immunoglobulin repertoire contribute to immunotherapy response; and how subversion of the immune repertoire can lead to pathogenesis. The laboratory is highly vested in their novel, high-throughput pipeline for defining the immunoglobulin repertoire and for rapidly and inexpensively creating custom, sequence-defined, recombinant antibodies.