B cells are lymphocytes of the Adaptive immune system that develop in the Bone marrow and mediate humoral immunity by differentiating into antibody‑secreting Plasma cells and long‑lived memory cells. In mammals, B‑cell development occurs in bone marrow; the letter “B” originated from the avian bursa of Fabricius, where the lineage was first identified in the 1960s through removal experiments that abolished antibody production. Encyclopaedia Britannica;
British Society for Immunology.
Structure and antigen receptor
- –Each B cell expresses a unique B‑cell receptor (BCR), a membrane‑bound immunoglobulin associated with the signaling heterodimer Igα/Igβ (CD79A/CD79B). The BCR recognizes native antigens; upon activation, the secreted form is the antibody.
Antibody;
PubMed.
- –Antibody molecules comprise two identical heavy chains and two identical light chains forming a Y‑shaped structure with variable antigen‑binding regions and constant effector regions that define classes (isotypes) such as IgM, IgG, IgA, IgE, and IgD.
Development and tolerance
- –B cells arise from hematopoietic stem cells and progress through pro‑B, pre‑B, immature, transitional, and mature stages. Antigen receptor diversity is generated by RAG1/2‑dependent V(D)J recombination.
NCBI Bookshelf – Janeway’s Immunobiology;
Annual Reviews.
- –Central tolerance eliminates or edits autoreactive clones in bone marrow via receptor editing, deletion, or anergy; peripheral tolerance further restrains autoreactive cells through anergy and inhibitory signaling.
JCI Insight;
Major subsets and phenotypes
- –Follicular (FO) B cells recirculate through Lymph node follicles and spleen, generating germinal center (GC) responses to T‑dependent antigens.
- –Marginal zone (MZ) B cells, positioned at the splenic marginal zone, respond rapidly to blood‑borne antigens and can mount T‑independent and T‑dependent responses.
Nature Reviews Immunology/PMC.
- –B‑1 cells (especially in peritoneal and pleural cavities) produce “natural” IgM and respond swiftly to pathogen patterns.
- –Common diagnostic markers include CD19 and CD20 on most mature B cells (but not on normal terminal plasma cells).
Mayo Clinic Laboratories.
- –Human memory B cells are often identified by CD27, though memory phenotypes are heterogeneous and CD27‑negative memory populations exist.
Activation and T cell help
- –B‑cell activation is typically T‑dependent: antigen‑specific B cells present processed peptide via MHC class II to T cells, receiving CD40L–CD40 co‑stimulation and cytokines (notably IL‑4, IL‑21) that promote proliferation, GC entry, and differentiation.
- –T‑independent activation (e.g., by polysaccharides with repetitive epitopes) can trigger antibody responses without T cell help, classically producing IgM and some long‑lived plasma cells.
Journal of Immunology.
- –B cells integrate innate signals through Toll‑like receptors (TLRs), which modulate extrafollicular and GC responses and can contribute to autoimmunity when dysregulated.
Germinal center reaction and antibody diversification
- –Within the Germinal center, activated B cells undergo clonal expansion, somatic hypermutation (SHM), and affinity‑based selection, yielding high‑affinity memory B cells and plasma cells.
- –Class‑switch recombination (CSR) and SHM require activation‑induced cytidine deaminase (AID/AICDA), which initiates targeted DNA deamination; AID deficiency causes hyper‑IgM syndrome type 2 and failure of SHM/CSR.
- –Cytokines steer isotype choice: IL‑4 promotes IgE/IgG1 (mouse), IFN‑γ promotes IgG2a (mouse), and TGF‑β favors IgA, with CD40–CD40L signaling essential for switching.
Effector and memory fates
- –Plasma cells secrete antibodies that neutralize pathogens, opsonize targets, and activate complement. Long‑lived plasma cells home to bone marrow niches supported by stromal factors (e.g., IL‑6, adhesion molecules).
- –Memory B cells persist with enhanced responsiveness on re‑exposure, providing rapid secondary responses; human memory compartments include class‑switched and IgM memory subsets.
Frontiers;
Antigen presentation by B cells
- –In addition to antibody production, B cells function as professional antigen‑presenting cells: BCR‑mediated antigen uptake targets peptides to MHC II compartments regulated by HLA‑DM and HLA‑DO, enabling efficient cognate help from T follicular helper cells.
British Society for Immunology.
Regulatory roles
- –Regulatory B cells (Bregs) suppress inflammation chiefly through IL‑10 and can promote tolerance in models of autoimmunity; multiple phenotypes and induction pathways are described in mice and humans.
Arthritis Research & Therapy.
Clinical significance
- –Primary immunodeficiencies of B‑cell development or function include X‑linked agammaglobulinemia (BTK deficiency) with absent mature B cells and severe hypogammaglobulinemia, and hyper‑IgM syndromes from defects in CD40L, CD40, or AID, which impair class switching and GC formation.
- –B‑cell malignancies encompass most non‑Hodgkin lymphomas (e.g., diffuse large B‑cell lymphoma, follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma), chronic lymphocytic leukemia, and others.
American Cancer Society;
Mayo Clinic.
- –Therapeutics targeting B cells include anti‑CD20 monoclonal antibodies such as rituximab for B‑cell lymphomas and certain autoimmune diseases; approved indications and safety (e.g., hepatitis B reactivation risk) are detailed by the U.S. FDA.
FDA;
Historical note
- –The “B” in B cell denotes the bursa of Fabricius in birds, whose removal abolished antibody formation; in humans and other mammals, B cells arise in bone marrow.
Related concepts and techniques
- –Monoclonal antibody technology exploits B‑cell specificity to generate defined antibodies for research and therapy.