About this Research Topic
B lymphocytes, identified more than half a century ago, are crucial for sustained host immune responses to pathogens through differentiation into long-lived plasma cells and memory B cells, particularly those producing specific antibodies of switched immunoglobulin (Ig) isotypes (IgG, IgA and IgE). Reflecting the diversity of microorganisms that they need to counter against, B cells function as both innate and adaptive immune cells, with their activation driven or fine-tuned by signals from a multitude of immune receptors, the number of which would rival that in any other cell types. Consequently, B cells significantly alter the network of signal transducers as well as transcription factors, thereby re-shaping their epigenome and transcriptome to affect the differentiation processes. In particular, new information has emerged on the mechanisms underlying the activation of NF-kB, a B cell-restricted nuclear factor specifically binding to an enhancer element in the Ig kappa light chain locus (hence the name) that was discovered almost as long ago as B cells themselves. How NF-kB - which together with Toll-like receptors (TLRs) forms the most ancient immune signaling module in eukaryotes - interacts with other signaling modules triggered by innate and adaptive receptors, such as those inducing AP-1, IRFs and T-bet, is also of significant importance.
New insights into how B cells respond to infections/re-infections have also been generated through the recent identification of B cell subsets with strong implications in host immunity against infectious agents, autoimmunity and aging, such as activation-induced naïve B cells, age-associated B cells and atypical memory B cells. Notably, some of these B cell subsets share the functional dependency on T-bet, but are distinct from each other, perhaps due to the differential targeting of NF-kB and IRFs. This is particularly pertinent to the understanding of B cell differentiation modulated by IFNy in the antibody and autoantibody responses. It has been increasingly appreciated that activation, proliferation and differentiation of B cells are tightly linked to and specifically regulated by the metabolic state of these cells. We emphasize the differential requirements of glycolysis for B cells to fast divide, a hypoxia environment for B cells to undergo CSR, and oxidative phosphorylation for B cells to differentiate into plasma cells. While hypoxia also promotes the survival of plasma cells, autophagy plays a crucial role in the generation and maintenance of class-switched memory B cells. Indeed, throughout all B cell activation and differentiation stages, different sophisticated mechanisms are employed to counter the propensity of B cells to death.
With novel tools that continuously provide newer and more accurate information, B cells have become the center of our attention due to insufficient vaccines and therapeutic means to endemics in the developing world, the hypersensitivity and intolerance in the developed world, and ill preparations to emerging infectious agents that can quickly turn to pandemics in both, with COVID-19 being a clear case.
Here, we seek Original Research, Review, Mini-Review, Hypothesis and Theory, and Opinion articles that cover, but are not limited to, the following subjects:
1. B cell and antibody responses to specific infectious agents during natural infections and in pre-clinical animal models.
2. Generation of memory B cells and development of vaccines against persistent and newly emerging infections.
3. Heightened antibody responses to allergens or autoantigens and underlying dysregulation of B cell activation and differentiation.
4. Complexity of B cell stimuli and their interactions, in the context of local and systemic immune environments, to regulate CSR, SHM and plasma cell differentiation.
5. Networks of signal transduction pathways and transcription factors that underpin the B cell response.
6. Regulation of B cell differentiation by metabolic, nutritional, hormonal and other environmental elements, and underlying epigenetic mechanisms.
7. Function of B cells as regulatory cells, in the context of cancer immunology, diabetes, gut inflammation and other pathophysiological conditions.
8. New clinical studies in B cell lymphomagenesis and autoimmune diseases built on the understanding of molecular mechanisms of B cell differentiation.
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