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 × 106/l) or without (1.7 × 106/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.

Regulatory B cells are enriched within the IgM memory and transitional subsets in healthy donors but are deficient in chronic GVHD

“…Chronic GVHD status at the time of sample collection was classified according to published criteria. 23,24 In keeping with previous reports, [25][26][27] Acute GVHD* Grade 0 7 (64) 3 (27) .37…”

“…Grades I-II 3 (27) 5 (46) Grades III-IV 1 (9) 3 (27) Donor lymphocyte infusions* The cohort includes patients who had received reduced intensity or myeloablative conditioning, followed by bone marrow or mobilized PB stem cell grafts. Those receiving high-dose steroids (.0.75 mg/kg prednisone) at the time of sampling or those who had received rituximab for any reason were excluded.…”

Sequential monitoring of lymphocyte subsets and of T-and-B cell neogenesis indexes to identify time-varying immunologic profiles in relation to graft-versus-host disease and relapse after allogeneic stem cell transplantation

“…Increased values of KRECs in cGVHD were never reported before, while there are few studies on the impact of GVHD on B cell generation [30–32]. The prevalence of immature B cells in PB was evidenced in autoimmune diseases and immunodeficiences, while their association with cGVHD is controversial [22,23,25,44,45]. Immature B cells elicit rapid antibody-dependent or -independent responses in absence of T cell induction, and are not completely depleted by CD20-targeted immunotherapy [51], partly explaining the incomplete responses observed in cGVHD.…”

Functional hyposplenism after hematopoietic stem cell transplantation

“…6 Improved splenic function was accompanied by a concomitant restoration of the IgM memory B-cell pool. 15 cGvHD is also associated with a lack of IgM memory B cells 16,17 suggesting the presence of pitted red cells may be a surrogate marker for B-cell dysfunction.…”