B lymphocyte reconstitution after hematopoietic stem cell transplantation: functional immaturity and slow recovery of memory CD27+ B cells

Functional recovery of B lymphocytes after hematopoietic stem cell transplantation (HSCT) can take up to 2 years. HSCT recipients may obtain protective titers of pathogen-specific antibody through vaccination, but optimal timing of reimmunization remains to be defined. In this study, we evaluated the reconstitution of B-cell number and activity in 139 children given HSCT, by B-cell subset phenotyping and in vitro immunoglobulin (Ig) production. Patients were longitudinally studied at 3, 6, 12, and 18 to 24 months after transplantation. At all time points, recipients displayed a significantly higher percentage of naive (IgD+CD27-) B cells and showed significantly lower production of stimulated in vitro Ig as compared to healthy controls. Moreover, during follow-up, we observed an increase in the proportion of patients who had CD27+ B subsets and who were able to mount in vitro Ig production greater than the 5th percentile. Similar to what has been described in adults, most children lack memory B cells and produce low amounts of Ig. However, the number of B cells, as well as their function, gradually recovered over time and the spread of data we observed suggests that the reimmunization schedule should be individualized for each patient. It remains to be defined in a prospective clinical study the time point at which a patient should start reimmunization. A reasonable hypothesis to be explored is the time point at which a percentage of memory B cells greater than the 5th percentile of normal controls is reached.