Unraveling B Cell Trajectories at Single Cell Resolution
Summary
Throughout adaptive immunity, B cells undergo differentiation that culminates in the generation of either memory B cells or plasma cells, which ultimately results in the production of antibodies directed against exogenous antigens for the purpose of combatting infection. Furthermore, B cells evince an antigen-presenting capacity and are critical participants in the activation of T cells during cellular immune responses. However, the disruption of their proper functional homeostasis can lead to a constellation of autoimmune disorders and malignancies. In light of the momentous progress achieved in the domain of single cell technologies, the exploration of B cells at the level of individual cells, incorporating genomics, transcriptomics, and proteomics, has generated a profoundly enriched understanding of the molecular underpinnings governing B cell development, differentiation, and the orchestration of their antibody repertoire, both in states of normalcy and in the context of infection and disease. In this review, we contemplate the adoption of single cell approaches in identifying distinctive B cell gene signatures and biomarkers in both normal and diseased tissues, with an eye to the ensuing therapeutic prospects that lie therein.
The role of B cells in adaptive immunity at the single cell level
B cells represent a vital component of adaptive immune responses, where their differentiation into plasma cells results in the production of antibodies of differing immunoglobulin isotypes that target and neutralize pathogens via diverse mechanisms. Importantly, B cells also generate memory cells to elicit subsequent immune responses upon re-exposure to the same antigen. However, the dysregulation of B cell function can lead to a host of ailments, including autoimmune diseases and malignancies. Thus, studying the various stages of B cell development, activation, and differentiation is key to understanding the underlying physiological mechanisms. The unique states of B cells in each anatomical niche further emphasize the importance of examining these cells using single cell methods. Such techniques encompass genomic, transcriptomic, and proteomic data analyses, and enable researchers to decipher B cell lineages, phenotype, interactomes, and plasticity at a single cell level. The results of these analyses can reveal specific gene expression signatures in B cells during normal and disease states, which may have implications for future therapeutic approaches. In this review, we discuss recent advances in the study of B cell biology using single cell approaches, with a focus on identifying distinct gene expression patterns in normal and diseased B cell populations, and highlight the potential of these methods in uncovering new therapeutic avenues.
Fig.1 B cell profiles in human germinal centers (GCs) generated via single cell approaches. (Morgan, 2022)
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Reference
- Morgan, D.; Tergaonkar, V. Unraveling B cell trajectories at single cell resolution. Trends in Immunology. 2022, 43(3): 210-229.
