Allogeneic Hematopoietic Stem Cell Transplantation Recipients Have Defects of Both Switched and IgM Memory B Cells

Allogeneic hematopoietic stem cell transplant (HSCT) recipients were assessed to elucidate memory B cell defects underlying their increased susceptibility to infections, particularly by encapsulated bacteria. Circulating IgM memory B cells (CD19⁺, CD27⁺, IgM⁺) and switched memory B cells (CD19⁺, CD27⁺, IgM⁻) were enumerated in allogeneic HSCT recipients (n = 37) and healthy controls (n = 35). T lymphocyte subpopulations and serum levels of immunoglobulins, including IgG subclasses, and antibodies to pneumococcal polysaccharides were also assayed. Allogeneic HSCT recipients were deficient in both switched memory and IgM memory B cells compared to healthy controls (both P < .0001), irrespective of time post-HSCT. Switched memory B cell deficiency correlated with CD4⁺ T cell deficiency, and both correlated with serum levels of IgG1 (P < .0001), possibly reflecting impaired B cell isotype switching in germinal centres. “Steady-state” serum levels of antibodies to pneumococcal polysaccharides did not correlate with circulating memory B cells. Graft-versus-host disease (GVHD) was associated with lower IgM memory B cell counts and lower serum levels of IgG2, IgG4, IgA, and pneumococcal antibodies. The increased susceptibility of allogeneic HSCT patients to infection may reflect a combination of memory B cell defects, which are most common in patients with a history of GVHD.

Key Words: HSCT, IgM memory and switched memory B cells, CD4⁺ T cells, Pneumococcal antibodies, GVHD