B cells defined by immunoglobulin isotypes.

The ability of B cells to generate antibodies and provide long-lived protective immunity is the cornerstone of vaccination and has contributed to the success of modern medicine. The nine different antibody subclasses produced by humans have effector functions that differ according to antigen type and route of exposure. Expression of the appropriate isotype is critical for effective humoral immunity, and it is becoming clear that subclass specificity is to some extent reflected at the cellular level. Understanding the mechanisms that govern the induction, expansion, and maintenance of B cells expressing different antibody subclasses informs the strategic manipulation of responses to benefit human health. This article provides an overview of the mechanisms by which the different human antibody subclasses regulate immunity, presents an update on how antibody subclass expression is regulated at the cellular level and highlights key areas for future research.

Immunoglobulin class-switch recombination: Mechanism, regulation, and related diseases.

Maturation of the secondary antibody repertoire requires class-switch recombination (CSR), which switches IgM to other immunoglobulins (Igs), and somatic hypermutation, which promotes the production of high-affinity antibodies. Following immune response or infection within the body, activation of T cell-dependent and T cell-independent antigens triggers the activation of activation-induced cytidine deaminase, initiating the CSR process. CSR has the capacity to modify the functional properties of antibodies, thereby contributing to the adaptive immune response in the organism. Ig CSR defects, characterized by an abnormal relative frequency of Ig isotypes, represent a rare form of primary immunodeficiency. Elucidating the molecular basis of Ig diversification is essential for a better understanding of diseases related to Ig CSR defects and could provide clues for clinical diagnosis and therapeutic approaches. Here, we review the most recent insights on the diversification of five Ig isotypes and choose several classic diseases, including hyper-IgM syndrome, Waldenström macroglobulinemia, hyper-IgD syndrome, selective IgA deficiency, hyper-IgE syndrome, multiple myeloma, and Burkitt lymphoma, to illustrate the mechanism of Ig CSR deficiency. The investigation into the underlying mechanism of Ig CSR holds significant potential for the advancement of increasingly precise diagnostic and therapeutic approaches.