The lack of memory B cells including T cell independent IgM+ IgD+ memory B cells in chronic graft-versus host disease is associated with susceptibility to infection

Abstract

The chronic graft-versus host disease (cGVHD) is associated with a perturbed B cell homeostasis and an increased infection rate. Aiming to determine the impact of lymphocyte subsets on cGVHD, blood samples from 98 patients at least 100 days following allogeneic haematopoietic stem cell transplantation (median 1066 days) were analyzed, serum levels of immunoglobulins measured and the incidence of severe infections retrospectively documented. Absolute CD19(+) B cell counts, including counts of immature (CD10(+) CD38(++) CD20(+) IgM(++)) and transitional (CD10(-) CD38(++) CD20(+) IgM(++)) as well as class switched memory (CD19(+) CD27(+) IgM(-) IgD(-)) B cells in patients with active cGVHD (n = 52) were significantly decreased as compared to those with inactive (n = 18) or without cGVHD (n = 28). In addition, nonclass switched IgM(+) memory B cells (CD19(+) CD27(+) IgM(+) IgD(+)) were absent in patients with cGVHD, but not in patients with inactive (0.4 × 10(6) /l) or without (1.7 × 10(6) /l) cGVHD (both P < 0.001). In line with these results we found significantly decreased lgG levels in patients with cGVHD, which was associated with a significantly higher rate of severe infections in cGVHD patients. Our data underline the close association of diminished B cell counts with cGVHD and the onset of severe infections. The lack of IgM(+) memory B cells in patients with cGVHD may indicate functional asplenia.