Abstract
B cells are central to adaptive immunity and their functions in antibody responses are exquisitely regulated. As suggested by recent findings, B cell differentiation is mediated by intracellular membrane structures (including endosomes, lysosomes, and autophagosomes) and protein factors specifically associated with these membranes, including Rab7, Atg5, and Atg7. These factors participate in vesicle formation/trafficking, signal transduction and induction of gene expression to promote antigen presentation, class switch DNA recombination (CSR)/somatic hypermutation (SHM), and generation/maintenance of plasma cells and memory B cells. Their expression is induced in B cells activated to differentiate and further fine-tuned by immune-modulating microRNAs, which coordinates CSR/SHM, plasma cell differentiation, and memory B cell differentiation. These short non-coding RNAs would individually target multiple factors associated with the same intracellular membrane compartments and collaboratively target a single factor in addition to regulating AID and Blimp-1. These, together with regulation of microRNA biogenesis and activities by endosomes and autophagosomes, show that intracellular membranes and microRNAs, two broadly relevant cell constituents, play important roles in balancing gene expression to specify B cell differentiation processes for optimal antibody responses.
Highlights
B lymphocytes are critical to immunity by mediating production of neutralization antibodies to infectious pathogens and tumor cells [1]
In T-dependent antibody responses, specific B cells are induced through cognate interaction, and engagement of CD40, which is constitutively expressed on B cells, by trimeric CD154 expressed by specific T helper (TH) cells [4]
Rab7 would regulate plasma cell survival, in addition to its major role in class switch DNA recombination (CSR)/somatic hypermutation (SHM), and the collaboration of different membranes in regulating B cell differentiation is suggested by the role of endoplasmic reticulum (ER) in endosome biogenesis [98]
Summary
B lymphocytes are critical to immunity by mediating production of neutralization antibodies to infectious pathogens and tumor cells [1] They develop through several highly regulated steps, first as pro-B cells and pre-B cells in the bone marrow, in which immunoglobulin (Ig) V(D)J DNA recombination occurs, and subsequently as immature B cell stages and mature B cells in the periphery. Activated B cells differentiate in germinal centers, the newly formed specialized microenvironment within secondary lymphoid organs [5] They undergo class switch DNA recombination (CSR) in the Ig heavy chain (IgH) locus to switch their BCR from IgM or IgD to, depending on eliciting stimuli, IgG, IgE, or IgA, which endows an antibody with different biological effector functions without changing antigen specificity [4]. We will discuss the notion that microRNA activities are reciprocally regulated by intracellular membranes, as part of the controlling mechanisms that fine-tune gene expression and buffer molecular aberrancies to ensure the specificity of B cell differentiation and functions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
