memory B cell

**Origin and development** - Naive B cells (IgM+/IgD+) in the follicle bind antigen via the BCR, internalize and present it on MHC II, and receive help from CD4+ T follicular helper (Tfh) cells (CD40–CD40L interaction plus cytokines such as IL-4, IL-21). - Activated B cells enter the germinal center of secondary lymphoid organs (lymph node follicles, spleen white pulp), where they undergo: - **Somatic hypermutation** (AID, activation-induced cytidine deaminase) of the variable region genes. - **Affinity maturation**: B cells with higher-affinity BCRs are selected by follicular dendritic cells and Tfh cells. - **Class switching** (AID plus cytokine signals) from IgM to IgG, IgA, or IgE. Requires CD40–CD40L. - Germinal center B cells then differentiate into either **long-lived plasma cells** (antibody secretion, home to bone marrow) or **memory B cells** (circulate and reside in lymphoid tissue).

**Key features** - Surface markers: CD19, CD20, CD27 (classic human memory marker), and MHC II. They express surface immunoglobulin (mostly class-switched, e.g., IgG), but do not secrete large amounts of antibody at rest. - Long-lived, quiescent, and have a lower activation threshold than naive cells. - Carry somatically mutated, higher-affinity BCRs. - Some memory B cells are T-independent (e.g., IgM+ memory cells), but the classic high-affinity, class-switched memory population is T-dependent.

**Primary vs. secondary response** - Primary response: lag of about 5-10 days, low titer, mainly IgM, lower affinity. - Secondary (anamnestic) response: shorter lag (about 1-3 days), higher titer, mainly IgG, higher affinity, and longer duration. Memory B cells rapidly proliferate and differentiate into plasma cells.

**Clinical significance** - **Vaccination**: The goal is to generate memory B cells and long-lived plasma cells. Boosters re-stimulate memory and further drive affinity maturation. - **Conjugate vaccines** (e.g., Hib, pneumococcal, meningococcal): The polysaccharide is conjugated to a protein carrier so that T cells provide help. This converts a T-independent response (IgM, no memory, poor in infants) into a T-dependent one with class switching and memory. - **Hyper-IgM syndrome** (CD40L or CD40 defect, AID defect): Impaired germinal center reaction. Patients have no class switching or memory formation, high IgM, and low IgG/IgA/IgE. They get recurrent pyogenic and opportunistic infections (e.g., Pneumocystis). - **Common variable immunodeficiency (CVID)**: Defective B cell differentiation, with low memory B cells and plasma cells. Presents with recurrent sinopulmonary infections and increased risk of autoimmunity and lymphoma. - **Rituximab (anti-CD20)**: Depletes naive and memory B cells (not plasma cells or pro-B cells, which lack CD20). It is used in lymphoma, RA, and ITP, among others. It impairs vaccine responses and can cause HBV reactivation. - **Memory B cell-derived malignancies**: Many lymphomas arise from germinal center or post-germinal center B cells. Examples are follicular lymphoma (t(14;18), BCL2), Burkitt (t(8;14), MYC), and DLBCL. Mantle cell lymphoma arises from naive/mantle zone cells (t(11;14), cyclin D1). Marginal zone lymphoma (e.g., MALToma) arises from memory B cells of the marginal zone. - **Autoimmunity**: Autoreactive memory B cells contribute to relapsing disease (e.g., SLE, myasthenia gravis, MS). - **Hapten/Rh sensitization**: A previous exposure to Rh+ blood can leave an Rh– mother with memory B cells, giving a strong IgG response in later pregnancies (hemolytic disease of the newborn). RhoGAM prevents this sensitization.

**High-yield contrasts** - Memory B cell vs. plasma cell: memory cells have surface Ig and express CD20 and MHC II; plasma cells secrete antibody, have abundant rough ER, lack CD20 and surface Ig, and express CD38 and CD138 (syndecan-1). - Memory B cells vs. memory T cells: B cells give antibody-mediated recall (humoral); T cells give cell-mediated recall (CD4 helper and CD8 cytotoxic). - Cell-mediated vs. humoral memory is clinically assessed by serology (IgG titers) for B cell memory.

**Mnemonic**: "Memory = Mutated + Maturated + Matched-class-switched." The germinal center makes memory B cells through SHM, affinity maturation, and class switching.