Blocking plasma cell fate enhances antigen-specific presentation by B cells to boost anti-tumor immunity

B cells engage in anti-tumor immunity but how they contribute to cancer suppression remains unclear. We found that inhibiting plasma cell differentiation either in IgMi mice lacking Igh elements needed for antibody secretion or in mice with B cell-specific knockout of Blimp-1 (Blimp-1 BcKO) promoted rather than inhibited antitumor immunity and increased numbers of activated B cells. Deficiency of Blimp-1 in tumor-infiltrating B cells generated a unique transcription profile associated with expansion of mutated clones targeting cognate tumor cells. Major histocompatibility complex class II (MHC II) was required for the anti-tumor efficacy. Blimp-1-deficient B cells had increased expression of CD80 and CD86 costimulatory molecules that enhanced effector T cell function. The Blimp-1 inhibitor valproic acid suppressed tumor growth in a B cell-dependent manner. Thus, inhibition of plasma cell differentiation results in enhanced tumor-specific antigen presentation by B cells and thereby tumor repression, suggesting a potential avenue of immunotherapy against cancer. Overall design: To explore the dynamics of tumor-infiltrating B cells, we generated single-cell RNA and B cell V(D)J libraries using a combination of sorted CD138+ and B220+ B cells from tumor-infiltrating lymphocytes (TILs) that were isolated from inoculated MC38 tumors on day 18 post-inoculation (DPI18).