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.
D'Orsogna
Lloyd J
LJ
Department of Clinical Immunology and Immunogenetics, Royal Perth Hospital and PathWest Laboratory Medicine, Perth, Australia.
Wright
Matthew P
MP
Krueger
Rom G
RG
McKinnon
Elizabeth J
EJ
Buffery
Susan I
SI
Witt
Campbell S
CS
Staples
Nicole
N
Loh
Richard
R
Cannell
Paul K
PK
Christiansen
Frank T
FT
French
Martyn A
MA
D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D018941:Antigens, CD19 / Q000097:blood / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003430:Cross-Sectional Studies; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte / Q000276:immunology*; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology*; D007156:Immunologic Memory; D008297:Male; D008875:Middle Aged; D011135:Polysaccharides, Bacterial / Q000276:immunology; D012189:Retrospective Studies; D013296:Streptococcus pneumoniae / Q000276:immunology; D014184:Transplantation, Homologous; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000097:blood / Q000276:immunology
D000907:Antibodies, Bacterial; D018941:Antigens, CD19; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011135:Polysaccharides, Bacterial; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7