Early Reconstitution of Antibody Secreting Cells after Allogeneic Stem Cell Transplantation

Martina Hinterleitner; Clemens Hinterleitner; Elke Malenke; Birgit Federmann; Ursula Holzer; Martin Müller; Wolfgang A Bethge; Stefan Wirths

doi:10.3390/jcm11010270

Early Reconstitution of Antibody Secreting Cells after Allogeneic Stem Cell Transplantation

J Clin Med. 2022 Jan 5;11(1):270. doi: 10.3390/jcm11010270.

Authors

Martina Hinterleitner^{1

2

3}, Clemens Hinterleitner^{1

2

3}, Elke Malenke⁴, Birgit Federmann^{1

5}, Ursula Holzer⁴, Martin Müller^{1

6}, Wolfgang A Bethge¹, Stefan Wirths¹

Affiliations

¹ Department of Hematology, Oncology, Clinical Immunology and Rheumatology, University Hospital Tuebingen, 72076 Tuebingen, Germany.
² Department of Medical Oncology & Pneumology (Internal Medicine VIII), University Hospital Tuebingen, 72076 Tuebingen, Germany.
³ DFG Cluster of Excellence 2180 'Image-Guided and Functional Instructed Tumor Therapy' (IFIT), University of Tuebingen, 72076 Tuebingen, Germany.
⁴ Department of Pediatric Hematology and Oncology, University Hospital Tuebingen, 72076 Tuebingen, Germany.
⁵ Department of Pathology and Neuropathology, University Hospital Tuebingen, 72076 Tuebingen, Germany.
⁶ Department of Hematology, Oncology and Immunology, Klinikum Region Hannover, KRH Klinikum Siloah, 30459 Hannover, Germany.

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^- CD38^low/+ 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.

Keywords: allogenic stem cell transplantation; hematology; immune cells; reconstitution.