Adaptive Immunity: B Cell Diversity, AID, Somatic Hypermutation, and Affinity Maturation

Overview

The Osmosis video explains how adaptive immunity achieves pathogen-specific responses through the diversity of B and T lymphocyte antigen receptors. It covers how VDJ rearrangement generates vast receptor repertoires, how B cells undergo class switching and affinity maturation, and how AID drives both processes. The content connects molecular events to functional antibody responses and clinical implications such as hyper IgM immunodeficiency caused by CD40 ligand defects.

It also contrasts surface B cell receptors with membrane-bound antibodies, describes the role of MHC class II in presenting antigen to helper T cells, and highlights how cytokines direct antibody class production and affinity optimization as infection is cleared.

Introduction to adaptive immunity and receptor diversity

The video opens by explaining that the immune response is highly specific for each invader because adaptive immune cells carry receptors that distinguish pathogens by their unique antigens. The key players are lymphocytes, especially B cells and T cells, which express B cell receptors (BCRs) and T cell receptors (TCRs). Through VDJ rearrangement, these receptors achieve immense diversity, enabling recognition of countless antigenic variants.

From receptor diversity to antibody classes

Each B cell receptor resembles an antibody but remains anchored to the B cell membrane. Receptors have a variable region that binds antigen and a constant region that defines antibody class, including IgM, IgG, IgA, IgD, and IgE. Activation of B cells begins when a foreign antigen cross-links adjacent BCRs, triggering signals that promote proliferation and differentiation. The B cell then internalizes the antigen and presents a fragment on MHC class II for recognition by a CD4+ helper T cell.

CD4+ T cell help and class switching

When a helper T cell binds the presented antigen, it expresses CD40 ligand, which engages the CD40 receptor on the B cell. This interaction, along with cytokines, activates AID (activation-induced cytidine deaminase), which drives class switching from IgM to IgG, IgA, or IgE. Mutations in the AID gene can lead to hyper IgM immunodeficiency, often caused by X-linked defects in CD40L that hinder CD40-B cell interactions.

Somatic hypermutation and affinity maturation

AID also promotes somatic hypermutation, a process that introduces targeted mutations in the BCR variable region. This occurs mainly in activated B cells within germinal centers of lymph nodes and spleen. AID converts cytidine to uridine in DNA, and the cell can repair these lesions via mismatch repair (MSH2/MSH6) or base excision repair (UNG), producing mutations that alter antigen-binding affinity. Some daughter cells acquire higher affinity for the antigen, a process known as affinity maturation, which resembles natural selection accelerated within a few days.

Balancing affinity and clinical relevance

As antigen levels decline during an infection, only B cells with the strongest binding survive, driving further optimization of antibody affinity. The BCR-variable-region mutations influence how tightly the receptor binds antigen, ultimately shaping the antibody repertoire as plasma cells secrete high-affinity antibodies. Hyper IgM immunodeficiency underscores the importance of the CD40-CD40L axis and AID-driven class switching in generating diverse, high-affinity antibody responses.

Recap

In summary, the video outlines the central steps of B cell–driven antibody responses: initial receptor diversification through VDJ rearrangement, T cell help guiding class switching, and somatic hypermutation in germinal centers that yields affinity-matured antibodies capable of efficiently targeting pathogens as antigen becomes limiting.