A BCR transgenic mouse model to study glycan-specific B cells

SUMMARY Tumor associated carbohydrate antigens (TACAs) are aberrant glycosylation products that are expressed on cancer cells but absent on most normal cells. Their expression is typically associated with metastasis, poor prognosis, and reduced overall survival. Our understanding of the mechanisms regulating antibody responses to TACAs is very limited. To overcome the limitations associated with studying the rare B cells that give rise to these responses, we generated a mouse in which the rearranged heavy chain variable region from a tumor glycan-reactive antibody was knocked into the endogenous heavy chain locus. We propose to characterize this mouse model by determining the potential for transgenic B cells to carry out antibody-dependent versus antibody-independent effector mechanisms in the productive anti-tumor response (Aim 1) and identify conditions which stimulate transgenic B cells to undergo isotype switching and differentiation to plasma cells (Aim 2). The findings emanating from these studies are expected to reveal novel strategies to harness the anti-tumor potential of B cells with specificities for cancer-expressed glycans.