Signal-transducing adaptor protein-2 delays recovery of B-lineage lymphocytes during hematopoietic stress

Signal-transducing adaptor protein-2 (STAP-2) was discovered as a C-FMS/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and I kappa B kinase in macrophages, mast cells, and T cells. There is additional information about roles for STAP-2 in several types of malignant diseases including chronic myeloid leukemia; however, none have been reported concerning B-lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this lack of knowledge, and demonstrated that STAP-2 is not required under normal, steadystate conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of B-cell lineage with myeloid rebound noted as unremarkable. Furthermore, all hematologic parameters were observed to be normal once recovery from transplantation was complete. In addition, overexpression of STAP-2, specifically in lymphoid cells, resulted in reduced numbers of late stage B-cell progenitors within the bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. Lipopolysaccharide (LPS) normally suppresses B precursor expansion in response to interleukin 7; however, STAP-2 deficiency made these cells more resistant. Preliminary RNA-sequencing analyses indicated multiple signaling pathways in B progenitors to be STAP-2-dependent. These findings suggest that STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could reveal ways to speed recovery of humoral immunity following chemotherapy or transplantation.