Development and Function of B Cell Subsets

doi:10.1016/B978-0-12-397933-9.00007-2

Molecular Biology of B Cells (Second Edition)

2015, Pages 99-119

https://doi.org/10.1016/B978-0-12-397933-9.00007-2 Get rights and content

Abstract

In the adult mouse, three major subsets of mature B-lymphocytes are recognized: B-1, marginal zone (MZ), and follicular (FO) B cells. These B lymphocytes are the products of B-cell precursors that follow developmental programs that require passage through successive checkpoints to produce appropriately matured B-cell clonotypes. Comparative studies of human subjects found patterns of development and subset composition that are similar, but not identical, to those observed in mice. This chapter focuses on the derivation, development, compartmentalization, and function of these three major B-cell subsets: B-1, MZ and FO. Discussion of the developmental fate of these cells after exposure to antigen, including germinal center formation, class switching, memory B cell, and plasma cell development, can be found in other chapters of this textbook.

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DnaJ homolog subfamily A member 3 (DNAJA3), also known as the tumorous imaginal disc (Tid1), is shown to be crucial in T cell development. DNAJA3 functions as a tumor suppressor implicated in lymphocyte development and survival. However, the role of DNAJA3 in B cell development and immune function remains unknown. In this study, we utilized a mouse model of B cell-specific DNAJA3 knockout (CD19-Cre/⁺; DNAJA3^flx/flx) to investigate the physiological function of DNAJA3 in B cell development and immune function.
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DNAJA3 deficiency decreases from pro B cells to immature B cells. The overall B220⁺ population in the bone marrow and secondary immune organs also decreased. B cell subpopulations B1 (B1b) and B2 significantly decrease. The B cell blastogenesis activity and immunoglobulin production decreased in DNAJA3 KO mice. Mechanistically, DNAJA3 deficiency significantly increases dysfunctional mitochondria activity and decreases mitochondrial mass, membrane potential, and mitochondria respiratory complex proteins. These factors could have influenced B cell differentiation during development, differentiation to antibody-secreting cells, and immune activation.
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The emerging repertoire consists of newly formed B cells in the primary lymphoid organs undergoing selection processes before reaching the peripheral naïve mature B cell pool. The available repertoire constitutes the mature naïve follicular, marginal zone, or B-1 B cells populating the peripheral lymphoid organs and tissues (reviewed in Ref [19]). The emerging and available repertoires exist largely in the context of surface-bound Ig on immature and mature naïve B cells, while the actual repertoire contributes to the pool of soluble antibody and memory B cells.
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Chapter 7 - Development and Function of B Cell Subsets

Abstract