Selecting B cells and plasma cells to memory

Humoral immunity appears to be based on immunological memory provided by memory plasma cells, which secrete protective antibodies, and memory B cells, which react to antigen challenge by differentiating into plasma cells. How these differentiation pathways relate to each other, how cells are selected into these memory populations, and how these populations are maintained remains enigmatic

Maintenance of quiescent immune memory in the bone marrow

The adaptive immune system has the important ability to generate and maintain a memory for antigens once encountered. Recent progress in understanding the organization of immunological memory has challenged the established paradigm of maintenance of memory by restless, circulating, and “homeostatically” proliferating lymphocytes. Among other tissues, the bone marrow has emerged as a preferred resting place for memory lymphocytes providing both local and systemic long‐term protection. Why the bone marrow? There, mesenchymal stromal cells provide a privileged environment for quiescent memory B and T lymphocytes, the protagonists of secondary immune reactions, and for memory plasma cells providing persistent humoral immunity. In this review, we discuss the dedicated role of the bone marrow for the maintenance of memory lymphocytes and its implications for immunological memory.DFG, 389687267, Kompartimentalisierung, Aufrechterhaltung und Reaktivierung humaner Gedächtnis-T-Lymphozyten aus Knochenmark und peripherem BlutEC/FP7/268987/EU/Protective and pathogenic immunological memory and its organisation by stroma cells/IMMEM

9‐cis Retinoic acid and 1.25‐dihydroxyvitamin D 3 drive differentiation into IgA + secreting plasmablasts in human naïve B cells

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