Abstract
Immune cell reconstitution after stem cell transplantation is allocated over several stages. Whereas cells mediating innate immunity recover rapidly, adaptive immune cells, including T and B cells, recover slowly over several months. In this study we investigated kinetics and reconstitution of de novo B cell formation in patients receiving CD3 and CD19 depleted haploidentical stem cell transplantation with additional in vivo T cell depletion with monoclonal anti-CD3 antibody. This model enables a detailed in vivo evaluation of hierarchy and attribution of defined lymphocyte populations without skewing by mTOR- or NFAT-inhibitors. As expected CD3+ T cells and their subsets had delayed reconstitution (<100 cells/μL at day +90). Well defined CD19+ B lymphocytes of naïve and memory phenotype were detected at day +60. Remarkably, we observed a very early reconstitution of antibody-secreting cells (ASC) at day +14. These ASC carried the HLA-haplotype of the donor and secreted the isotypes IgM and IgA more prevalent than IgG. They correlated with a population of CD19− CD27− CD38low/+ CD138− cells. Of note, reconstitution of this ASC occurred without detectable circulating T cells and before increase of BAFF or other B cell stimulating factors. In summary, we describe a rapid reconstitution of peripheral blood ASC after CD3 and CD19 depleted haploidentical stem cell transplantation, far preceding detection of naïve and memory type B cells. Incidence before T cell reconstitution and spontaneous secretion of immunoglobulins allocate these early ASC to innate immunity, eventually maintaining natural antibody levels.
Highlights
Immune cell reconstitution after hematopoietic stem cell transplantation (HSCT) has major influence on control of bacterial, viral and fungal infections, on graft-versus-host disease (GvHD) and on graft-versus-leukemia/lymphoma (GvL) effects [1,2]
Even if the existence of a small fraction of plasma cells might be a potential source of bias in our setting, early antibody-secreting cells (ASC) developed independently from T cells and cytokines associated with the development of B cells and well characterized plasmablasts or long-lived plasma cells
They might represent a so far undescribed population of innate-like B cells. This hypothesis is further supported by the finding, that reconstitution of these cells was accompanied by an increase of IL-5, which has been described to be involved in a T cell-independent development of innate-like B cells and consecutive Ig production [22]
Summary
Immune cell reconstitution after hematopoietic stem cell transplantation (HSCT) has major influence on control of bacterial, viral and fungal infections, on graft-versus-host disease (GvHD) and on graft-versus-leukemia/lymphoma (GvL) effects [1,2]. It may give insight into fate decisions of hematopoietic stem cells in reconstitution of innate and adaptive immunity. A minute subset of circulating CD19+ B cells with the above characteristics are detected, carrying a CD20+ CD27+ CD43+ CD70− phenotype [12] It is yet undefined whether recovery of lymphoid cells follow the same hierarchy of primary innate type followed by adaptive lymphocyte reconstitution
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
