B-cell immunity after allogeneic hematopoietic cell transplantation.

Abstract

frequency of somatic mutations. Upon in vitro polyclonal stimulation, B-cell proliferation and IgM production are near-normal, whereas IgG and IgA production is low. This is most likely due to the low frequency of circulating isotype-switched or somatically mutated B cells, which, in turn, may be related to the relative absence of germinal centers in the spleen and lymph nodes. The cause of the relative lack of germinal centers is unknown, but could possibly be due to a shortage of helper T cells or follicular DCs. B cells are of donor origin (after myeloablative, T-cell replete HCT). Plasma cells appear to be primarily of host origin in the first few months after grafting. They are gradually replaced by plasma cells derived from donor B cells over the subsequent months to years. Whether these B cells originate from the grafted stem or B cells has not been directly studied. Circumstantial evidence suggests that by 4‐6 months after grafting the majority of B cells have been generated de novo (from stem cells). Ab levels and Ab responses to immunization reflect the number and function of B cells in concert with plasma cells, helper T cells, follicular DCs and other cells involved in the generation of Abs. In the first month after grafting, total IgM, IgG and IgA levels fall and reach their nadir near the low normal limit. They return to the normal range over the subsequent months to years, IgM first, and IgG 2 and IgA last. Specific Ab levels (e.g. against pneumococci) after grafting are higher in patients with high Ab levels pretransplant, transplanted from donors with high Ab levels pretransplant. In cases of recall protein Ags and polysaccharide‐protein conjugate Ags, the post-transplant Ab levels can be substantially increased by immunizing the donor before transplant, and the recipient peritransplant/early post-transplant. Improvement of B-cell immunity will probably come from one of the following: n Improved understanding and modulation of the presumed defect of naive to memory B-cell differentiation n Improved understanding and modulation of the suppressive effect of GvHD or GvHD therapy on Blymphopoiesis