Introduction

B cells or B lymphocytes (bursa-derived cells) are essential components of adaptive immune response, primarily responsible for humoral immunity in mammals. B-cell production in humans is a lifelong process that starts in the foetal liver, intrauterine, and bone marrow after birth.

B cells arise from hematopoietic stem cells (HSCs) and go through several stages of early differentiation, through maturation, antigen interaction and antibody synthesis. Through their early differentiation they acquire two key features of adaptive immunity, firstly the ability to distinguish between self and non-self, and the ability to form memory of previous antigen encounters.

In Max Cooper's 1960s experiments on chickens, antibody production was found to be impaired upon the removal of an organ known as the bursa of Fabricius, hence the term bursa-derived cells. However, in humans B cell development occurs predominantly in the bone marrow.

Differentiation and Development

Origins and Early Development

B lymphocytes arise from hematopoietic stem cells (HSCs) in the fetal liver, before shifting to the bone marrow after birth, the primary lymphoid organ in humans and most mammals. Non-lymphoid stromal cells within the bone marrow supply critical molecules including IL-7, cytokines, and adhesion molecules that support B-cell survival and ongoing differentiation, ensuring a continuous supply of B cells capable of recognising a limitless range of antigens.

Surface Markers and Checkpoints

B cell differentiation is characterised by specific surface (CD) markers and immunoglobulin gene rearrangements. Developmental checkpoints occur throughout the pathway, determining whether a cell proceeds normally or is directed toward an alternative fate, including programmed cell death.

Negative Selection and Self-Tolerance

During development, B cells undergo negative selection to eliminate self-reactive clones and prevent autoimmunity. However, since not all self-antigens are present in the bone marrow, additional peripheral tolerance mechanisms are required. Mature B cells that encounter self-antigens outside the bone marrow without appropriate T cell help undergo either anergy or clonal deletion.

T Cell Dependence and Thymus-Independent B Cells

Most mature B cells require T-helper cell signals to produce antibodies. A distinct subset thymus-independent (T-independent) B cells can respond to certain antigens without T-cell assistance, representing an alternative activation pathway.

Peripheral Circulation and Antigen Encounter

Surviving B cells migrate to peripheral lymphoid organs to await antigen exposure. Lymphoid follicles in these secondary lymphoid organs provide a specialised environment, housing follicular dendritic cells that present antigens to naïve B cells. Antigen sources vary by tissue location:

• Spleen: filters blood-borne antigens
• Lymph nodes: trap antigens from the lymphatic system
• Mucosa-associated lymphoid tissue (MALT): samples antigens from surrounding mucosal epithelium

B cells that fail to encounter antigen undergo programmed cell death, ensuring only antigen-responsive cells persist.

Locations

B cells are mainly found in the cortex of lymph nodes, and form part of the B cell follicles. There are two types of follicles; primary follicles which are small and uniform, containing naïve or resting B cells and secondary follicles which contain a germinal center, where B cells undergo activation, proliferation, and differentiation into plasma cells or memory B cells.
The germinal center contains a light zone of centrocytes, and a dark zone of centroblasts.

B cells are also located in the white pulp of the spleen, specifically periarteriolar lymphoid sheaths and follicles, similar to lymph nodes. They're also common in mucosa-associated lymphoid tissue, including in the tonsils and Peyer's patches, where they also form germinal centers.

Functions

Regulatory Cells

Generally, B cells are key regulatory cells in the immune system, producing antibodies and antigen-presenting cells, supporting other mononuclear cells, and directly contributing to inflammatory pathways.

B cells regulate the production of antigen specific immunoglobulins, directed against invasive pathogens (antibodies). They recognise antigens through membrane bound B cell receptors (BCR), and accessory cell surface receptors.

Antigen Recognition, Response and Memory

When stimulated by an antigen, B cells mature into plasma cells, synthesising five different classes of antibodies (IgG, IgA, IgM, IgE, IgD). After this occurs, the activated B cell undergoes mitotic division, producing clone cells that make the same antibodies with the same antigen specificity.

Upon encountering an antigen for the first time, B cells undergo the primary immune response. A few subsets of this clone mature into memory cells, which respond rapidly upon subsequent exposures to the same antigen, leading to a secondary immune response.

The secondary immune response is a higher magnitude, quicker, and produces IgG instead of IgM. This memory is the basis for lifelong immunity and vaccination.

Mediation and Regulation

B cells are responsible for many aspects of immune homeostasis. Experimental results in mice show that abnormalities in B cells result in reduced T cell numbers and diversity, absence of Peyer's Patch organogenesis, and defects in dendritic cells.

B cells are necessary for immune system maintenance. For example, B cells release immunomodulatory cytokines that influence immune cell functions of T cells and dendritic cells and regulate lymphoid tissue organogenesis, wound healing, and transplanted tissue rejection.

They are also essential in production of IL-10 which regulates T cell mediated inflammatory responses.

Sources

*Althuwaiqeb, S. A., & Bordoni, B. (2020). Histology, B Cell Lymphocyte. Retrieved from PubMed website: https://www.ncbi.nlm.nih.gov/books/NBK560905/

*Decker, J. (n.d.). B Cell Development. Retrieved May 25, 2026, from www2.nau.edu website: https://www2.nau.edu/~fpm/immunology/Exams/Bcelldevelopment-401.html

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