An introduction to the immune system’s B cells

We asked Dr Luke Muir, our Senior Study Scientist and B cell specialist, to tell us more about the underrated cells of the immune system. 

What are B cells?

B cells are specialised adaptive immune cells responsible for mediating humoral immunity. They are different from other immune cells in their unique expression of the B cell receptor (BCR), better known as antibody when produced in its soluble form. While research may focus on harnessing the capabilities of T cells, B cells also play a central role in the adaptive immune system. 

Individual B cells produce only one specific antibody (although they can produce thousands of copies of this antibody!). Through genetic recombination, it is theorised that our immune system can craft an astounding 10²⁵ different antibodies using a finite set of genes. Each antibody is meticulously tailored to recognise specific structural or linear epitopes, binding to native antigens and forming a frontline defence. 

B cell differentiation 

B cells with self-reacting antibodies are deleted through a stringent selection process. B cells that pass this checkpoint patrol peripheral tissue, blood, and lymphatics systems, waiting to be activated by foreign antigens. 

Upon encountering foreign antigens and receiving signals from activated CD4+ T cells, B cells typically embark on one of two differentiation pathways:

• Direct differentiation into antibody-secreting cells (ASCs), known as plasmablasts. These provide a surge of low-affinity antibodies specifically tailored to recognise and bind to antigens.

• The more complex route is through the germinal centre, a specialised structure where antigen-activated B cells undergo the process of immunoglobulin gene somatic hypermutation (SHM). SHM introduces random point mutations in the BCR. These mutations can either diminish or enhance the affinity of the BCR to antigens. The highest-affinity BCR-encoding B cells are positively selected – a cellular-level replication of Darwinian evolution.

Following this process, some antigen-specific B cells differentiate into high-affinity plasmablasts, returning home to the bone marrow to become plasma cells. Others transform into a long-lived memory B cell population that can rapidly respond to the reinfection of pathogens they have evolved to recognise. 

Figure 1: Adapted from [Nutt et al., Nature Reviews Immunology, 2015]. Generated using Biorender¹

Influence on the immune response

The multifaceted role of B cells extends beyond simply antibody secretion. Following their activation, B cells influence the immune response through several different effector functions, including:

Antibody secretion: The primary function of B cells is to secrete antibodies tailored to their specific targets. These antibodies can directly neutralise threats or mark them for destruction by other immune cells.

Antigen presentation: B cells double as professional antigen-presenting cells, acquiring specific antigens through their BCR. They internalise and process these antigens, presenting them to induce T cell activation.

Cytokine secretion: B cells wield influence over other immune cell subsets through cytokine production. They can produce regulatory cytokines like IL-10 and IL-35 or pro-inflammatory cytokines such as IL-6 and IFN-γ, thereby shaping the broader immune response.

The benefits of B cells 

B cells are mainly known for forming protective responses against infectious agents. Plasma cells guarantee a constant production of soluble antibodies, poised to either neutralise or label foreign antigens for elimination. In the event of a subsequent encounter with the same antigen, memory B cells orchestrate a focused and efficient immune response. 

The importance of the humoral immune response, mediated by B cells, is highlighted by the fact that all routine vaccines (except for the BCG vaccine) are thought to protect against infection via the induction of antibodies. Vaccines also depend on the establishment of immunological memory. 

B cells and antibodies can defend against other threats, including cancer. Antibodies can identify neoantigens present on cancerous cells, and compelling evidence links their presence to improved outcomes in specific cancer types. This intriguing connection has driven the development of cancer vaccine research. 

Can B cells cause harm? 

While B cells play a crucial role in defending the body against infections and other threats, their responses can sometimes be detrimental – leading to conditions like autoimmunity and cancer. 

B cells may mistakenly recognise and produce antibodies against self-antigens, sparking a misguided attack against the body's own tissues. This can result in chronic inflammation and tissue damage, characterising autoimmune diseases like rheumatoid arthritis, lupus, and multiple sclerosis.

In cancer, B cells may also contribute to harmful responses. Instead of effectively targeting cancer cells, B cells can sometimes become dysfunctional, promoting tumour growth and evading the immune system's surveillance. Some cancers even manipulate B cells to create a tumour-friendly environment, using the body's own defence mechanisms to their advantage. 

Understanding the dual nature of B cell responses is crucial for developing therapeutic strategies. While B cells can be a powerful tool in cancer immunotherapy, mitigating their harmful effects in autoimmunity is equally important. Maintaining this balance is challenging but essential in the quest for effective treatments against autoimmune diseases and cancer.