Immune recovery after stem cell transplantation proceeds in distinct phases. While components of the innate immune system re-emerge quickly, adaptive lymphocytes—particularly T and B cells—require several months to fully reconstitute. In this study, we examined the dynamics and regeneration of newly formed B cells in patients undergoing CD3- and CD19-depleted haploidentical stem cell transplantation combined with additional in vivo T-cell depletion using a monoclonal anti-CD3 antibody. This transplantation strategy provides a unique opportunity to analyze the hierarchy and contribution of specific lymphocyte subsets in vivo without the confounding effects of mTOR or NFAT inhibitors. As anticipated, CD3⁺ T cells and their subsets showed markedly delayed recovery, remaining below <100 cells/µL through day +90. Distinct naïve and memory CD19⁺ B-cell populations became detectable around day +60. Unexpectedly, we identified a very early emergence of antibody-secreting cells (ASC) as early as day +14. These ASC expressed the donor’s HLA haplotype and predominantly produced IgM and IgA, with lower levels of IgG. Their appearance was associated with a CD19⁻ CD27⁻ CD38low/+ CD138⁻ cell population.
Importantly, this ASC recovery occurred in the absence of circulating T cells and prior to any rise in BAFF or other B-cell–stimulating cytokines. In conclusion, we report a rapid restoration of peripheral ASC following CD3- and CD19-depleted haploidentical stem cell transplantation, well before the emergence of naïve or memory B cells. The early timing, independence from T-cell help, and spontaneous immunoglobulin secretion suggest that these ASC represent an innate-like population that may contribute to maintaining natural antibody levels during early immune reconstitution.
