germinal center B cell differentiation

Definition

Target type: biologicalprocess

The process in which a B cell in the spleen acquires the specialized features of a germinal center B cell. Germinal center B cells are rapidly cycling B cells which have downregulated IgD expression and exhibit high levels of binding by peanut agglutinin (PNA). [GOC:jal, ISBN:0781735149]

Germinal center (GC) B cell differentiation is a critical process in adaptive immune responses, leading to the generation of high-affinity antibody-producing plasma cells and memory B cells. It occurs in specialized microenvironments within secondary lymphoid organs, primarily lymph nodes and the spleen. The process is initiated by the activation of naive B cells by antigen-presenting cells (APCs), which triggers their migration into follicles. Within the follicle, activated B cells encounter antigen-specific T follicular helper (Tfh) cells, leading to the formation of GCs. GCs are characterized by a dynamic interplay between B cells, Tfh cells, and follicular dendritic cells (FDCs).

The differentiation of B cells within GCs is a multi-step process involving:

1. **Entry into the GC:** Activated B cells enter the GC, where they undergo rapid proliferation and somatic hypermutation (SHM) of their immunoglobulin (Ig) genes. This introduces mutations in the variable regions of Ig genes, resulting in a diverse pool of B cells expressing antibodies with varying affinities for the antigen.

2. **Selection and affinity maturation:** B cells compete for limited amounts of antigen presented on FDCs. B cells that bind the antigen with higher affinity are preferentially selected for survival and further proliferation. This process, known as affinity maturation, drives the evolution of B cells with progressively higher antigen binding affinity.

3. **Differentiation into plasma cells or memory B cells:** Following several rounds of proliferation and affinity maturation, GC B cells differentiate into either plasma cells or memory B cells. Plasma cells migrate to bone marrow or other sites of antibody production and secrete high-affinity antibodies. Memory B cells are long-lived cells that can rapidly differentiate into plasma cells upon re-exposure to the antigen, providing long-term immunity.

Key factors regulating GC B cell differentiation include:

* **B cell receptor (BCR) signaling:** Engagement of the BCR by antigen triggers a signaling cascade that promotes B cell survival, proliferation, and differentiation.
* **Tfh cell interactions:** Tfh cells provide essential signals, including cytokines such as IL-21, IL-4, and IL-6, that drive B cell differentiation and antibody production.
* **FDC interactions:** FDCs provide a platform for antigen presentation and regulate B cell survival and differentiation.
* **Cytokine milieu:** The cytokine environment within the GC influences the fate of B cells, determining whether they differentiate into plasma cells or memory B cells.

GC B cell differentiation is a highly regulated process that ensures the generation of high-affinity antibody responses against specific antigens. It plays a crucial role in maintaining long-term immunity and protecting against infectious diseases.'
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Proteins (2)

Compounds (12)