What's atypical about human B cells after allogeneic stem cell transplantation?

Atypical B cells or age-associated B cells represent an alternative lineage of memory B cells. Emerging evidence suggests that context influences the apparent functional heterogeneity of age-associated B cells. While data support a protective role for age-associated B cells in the setting of infection, multiple other studies suggest that these cells play a pathogenic role in the setting of autoimmunity. After treatment with allogeneic hematopoietic stem cell transplantation, the memory B-cell compartment is altered in patients who develop an autoimmune-like syndrome called chronic graft-versus-host disease. Patients with chronic graft-versus-host disease have significantly increased proportions of CD11c+ age-associated B cells within the peripheral compartment that develop under constant exposure to host alloantigens and persist under conditions when B-cell tolerance is not achieved. Herein, we review what is currently known about the molecular alterations in the heterogeneous memory B-cell compartment of hematopoietic stem cell transplantation patients, especially patients with chronic graft-versus-host disease who have developed autoimmune manifestations. In this mini-review, we summarize intrinsic factors in age-associated B cells found in autoimmune states that likely influence their extrafollicular localization, differentiation potential into autoantibody-secreting cells, and function. We highlight lessons from B-cell studies in chronic graft-versus-host disease to provide unique insights into the molecular underpinnings of the diverse functions of age-associated B cells.