Acquisition of Ig isotype diversity after bone marrow transplantation in adults. A recapitulation of normal B cell ontogeny.

To gain insight into the prolonged susceptibility to infections noted after allogeneic bone marrow transplantation (BMT), multiple parameters of the humoral immune system were serially monitored in ten bone marrow recipients. IgM B cells appeared in the circulation 2 to 4 mo after engraftment. During the first 6 mo, the IgM B cells expressed low levels of CD21 (C3d/EBV receptors) and were largely CD38+. IgG and IgA B cells were also found to coexpress surface IgM and IgD, indicating that they may be involved in a process of isotype switch. These features are characteristic of neonatal B cells. To explore the pattern of Ig isotype switch, the emergence of plasma cell precursors for each of the four IgG subclasses was examined by culturing blood lymphocytes with PWM or LPS and enumerating bone marrow plasma cells. A marked IgG2 and IgG4 plasma cell deficiency and a relative increase in IgG1 and IgG3 plasma cells were detected both in vitro and in vivo. Serum IgG2 and IgG4 levels were deficient for more than 18 mo after BMT, elevated IgG1 levels accounting for the normal or increased levels of total IgG. The data suggest that a selective unresponsiveness to polysaccharide Ag and IgG2 subclass deficiency may contribute to the late bacterial infections in BMT recipients. These features of gradual development of the humoral immune system in adults undergoing successful marrow engraftment reproduce some of the maturational steps that occur during normal B cell ontogeny over the first 1 to 2 yr of life.

Imbalances within the peripheral blood T-helper (CD4+) and T-suppressor (CD8+) cell populations in the reconstitution phase after human bone marrow transplantation.

Peripheral blood T cell subsets were evaluated in 11 patients during the reconstitution phase after allogeneic bone marrow transplantation and compared with 11 age-matched controls. The proportion of cells coexpressing Leu7 and CD11b (C3bi receptor) markers was determined within the CD4+ (T-helper) and the CD8+ (T-suppressor) subsets by two-color immunofluorescence analysis. CD4+ and CD8+ T cells reached normal or near-normal values within the first year posttransplant. In contrast to normal controls, however, most of the cells in both subsets coexpressed the Leu7 and CD11b markers. T cells with such phenotype display the morphological features of granular lymphocytes (GLs) and a functional inability to produce interleukin 2 (IL 2). These T cell imbalances were not related to graft v host disease (GvHD) or to clinically detectable virus infections and may account for some defects of cellular and humoral immunity that occur after bone marrow transplantation.