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9‐ cis Retinoic acid and 1.25‐dihydroxyvitamin D 3 drive differentiation into IgA + secreting plasmablasts in human naïve B cells
Author(s) -
Treptow Sandra,
Grün Joachim,
Scholz Josephine,
Radbruch Andreas,
Heine Guido,
Worm Margitta
Publication year - 2021
Publication title -
european journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.272
H-Index - 201
eISSN - 1521-4141
pISSN - 0014-2980
DOI - 10.1002/eji.202048557
Subject(s) - calcitriol , biology , retinoic acid , immune system , calcitriol receptor , microbiology and biotechnology , secretion , cellular differentiation , receptor , antibody , transcription factor , immunology , endocrinology , cell culture , biochemistry , vitamin d and neurology , genetics , gene
Abstract Calcitriol and 9‐cis retinoic acid (9cRA) play a fundamental role in shaping the adaptive immune response by altering the Ig profile and the differentiation of B cells, controlled by their corresponding nuclear receptors, VDR and RAR. Herein, after the establishment of a plasmablast differentiation culture, we investigated how both ligands modulate human naïve B cell differentiation and to which extent VDR/RXR and RAR/RXR signaling interferes. Calcitriol and 9cRA mediated activation of purified naïve B cells resulted in a strong differentiation of CD27 + CD38 + plasmablasts and antibody secretion. The significant IgA response was preceded by a strong induction of α‐germline transcription (GLT). Induction of αGLT and consecutively IgA secretion driven by calcitriol is a novel observation and we show by magnetic chromatin IP that this was mediated by recruitment of the VDR to the TGF‐β promoter thus inducing TGF‐β expression. Finally, as revealed by transcriptomic profiling calcitriol and 9cRA modulate several signals required for differentiation and isotype switching in a noncompeting but rather additive manner. Calcitriol and 9cRA participate in the control of the IgA response in human activated naïve B cells. The balance between both ligands may be an important factor in channeling humoral immune responses toward a protective direction.