8016 Background: B cells are critical to inhibiting tumor progression, as they generate tumor-reactive antibodies; promote anti-tumor killing capacity of NK cells and phagocytosis of macrophages/DCs; and enrich priming of T cells against the tumor. Multiple myeloma (MM) is a B-cell-derived malignancy, and its survival is partly driven by a deficiency in the immune response. Yet, the abnormalities of the B-cell-mediated humoral responses in MM are ill defined. Methods: We investigated B cell composition in bone marrow (BM) from patients with newly diagnosed MM (NDMM, N = 170), relapsed refractory MM (RRMM, N = 140) and healthy donors (HD, N = 21) by multi-color flow cytometry. Results: We observed that B1b cells was significantly reduced by 45% (p = 0.004) in NDMM patients compared to HD. B1b cells are important in generating long-lasting protective antibodies, particularly against vaccines, in a T cell independent fashion. Similarly, B2 cells, which can produce all antibody types, were