CD38 Defines a Subset of B Cells in Rainbow Trout Kidney With High IgM Secreting Capacities.

Diana Martín,Esther Morel,J. German Herranz-Jusdado,Irene Soleto,Patricia Díaz-Rosales,Luis A. Ramón,Beatriz Abós,Carolina Tafalla,Pedro Perdiguero,Tiehui Wang

doi:10.3389/fimmu.2021.773888

Abstract

CD38 is a multifunctional molecule that functions both as a transmembrane signaling receptor and as an ectoenzyme with important roles in cell adhesion, calcium regulation and signal transduction. Within the B cell linage, CD38 is expressed in diverse murine B cell subsets, with highest levels in innate B cell subpopulations such as marginal zone (MZ) B cells or B1 cells. In humans, however, CD38 is transiently expressed on early lymphocyte precursors, is lost on mature B cells and is consistently expressed on terminally differentiated plasma cells. In the present work, we have identified two homologues of mammalian CD38 in rainbow trout (Oncorhynchus mykiss), designating them as CD38A and CD38B. Although constitutively transcribed throughout different tissues in homeostasis, both CD38A and CD38B mRNA levels were significantly up-regulated in head kidney (HK) in response to a viral infection. In this organ, after the generation of a specific monoclonal antibody (mAb) against CD38A, the presence of CD38A+ populations among IgM+ B cells and IgM- leukocytes was investigated by flow cytometry. Interestingly, the percentage of IgM+CD38A+ B cells increased in response to an in vitro stimulation with inactivated Aeromonas salmonicida. Finally, we demonstrated that HK IgM+CD38A+ B cells had an increased IgM secreting capacity than that of cells lacking CD38A on the cell surface, also showing increased transcription levels of genes associated with B cell differentiation. This study strongly suggests a role for CD38 on the B cell differentiation process in teleosts, and provides us with novel tools to discern between B cell subsets in these species.

Highlights

Different B cell subsets are defined in mammals
In humans, terminally differentiated plasma cells express the highest levels of surface CD38 [24]
Cells to secrete IgM, we studied in these cells the levels of transcription of a selection of genes implicated in the differentiation of B cells to plasmablasts/plasma cells (PCs), comparing them to those obtained in IgM+CD38A- B cells

Summary

Introduction

Different B cell subsets are defined in mammals. These include follicular (FO) B2 cells (conventional B cells), B1 cells and marginal zone (MZ) B cells. CD38+ B Cells in Rainbow Trout these sites, B cells receive co-stimulatory signals from T follicular helper cells (Tfh) and specialized follicular dendritic cells (fDCs) and differentiate to antibody-secreting cells (ASCs), plasmablasts and eventually terminally-differentiated plasma cells (PCs) Throughout this differentiation process some cells become memory B cells. SHM results in an increased diversity of the antibody pool after which only B cells with higher affinity are selected by the antigen This diversification of Ig genes is critical for the generation of an adequate specific immune protection [2]. In contrast to conventional B2 cells, MZ B cells and B1 cells are usually considered elements of the innate immune system, being globally designated as innate B cells [3] These innate B cell populations mount extrafollicular immune responses outside the GCs in the absence of cognate T cell cooperation. B1 cells are mainly found in the peritoneal and pleural cavities, mucosal surfaces and spleen, but are absent or scarce in lymph nodes and peripheral blood [7, 8]

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Conclusion