Allogeneic hematopoietic cell transplantation (HCT) offers a unique opportunity to monitor the development of immune reconstitution using the patient as his or her own control. Furthermore, the donor serves as an HLA-identical normal control and source of adoptive immune transfer. Donor hematopoietic stem cells (HSCs) differentiate and proliferate to repopulate all blood lineages providing normal cell numbers of red blood cells, platelets, and neutrophils. Successful immune reconstitution and protection from infection requires antimicrobial B cell and antibody development. Studies of B cell reconstitution after HCT have primarily examined immunoglobulin concentration, B cell quantification, and antimicrobial antibody development in relation to donor/recipient serologic status or vaccination. Following HCT, humoral immunity has 3 distinct contributions. First, recipient antibody persists with an average half-life of 30-60 days, and some recipient plasma cells persist for years following allogeneic HCT [1] providing protective antimicrobial humoral immunity [2]. Some recipient antidonor alloimmune responses are detrimental contributring to primary graft rejection [3, 4] and prolonged red cell aplasia when donors and recipients are ABO major mismatched [5, 6]. Second, donor grafts contain naıve and memory B cells that have already undergone positive and negative selection in the HLA-identical donor and contribute adoptive antimicrobial and alloreactive B cells. Third, B cells reconstituting from donor HSCs recognizing disparate recipient antigens as ‘‘self’’will be clonally deleted, preventing alloreactive responses, but remain capable of responding to infectious challenges and vaccinations. This educational session will consider B cell responses following allogeneic HCT as they contribute to (1) vaccine-induced antimicrobial immunity,(2) autoimmune responses, and (3) allogeneic antibody responses. We will discuss a B cell role in chronic graft-versus-host diease (cGVHD) pathogenesis, review anti-B cell cGVHD therapy using rituximab, and, finally, consider the pathogenic role of agonistic antibodies targeting platelet-derived growth factor receptor (PDGFR).