What Are Atypical B Cells and What Is Their Health Impact?

The human immune system is a complex network of cells that defends the body against germs. A central part of this defense is the B cell, a type of white blood cell tasked with producing proteins called antibodies that recognize and neutralize specific threats. While conventional B cells are a foundation of immunity, scientists have identified a distinct variant, called atypical B cells, that operates differently. These cells are not just a minor variation; they represent a unique population that emerges under specific circumstances. Their presence can have significant implications for how the immune system responds to long-term challenges, making them an area of growing interest in medical research.

What Makes a B Cell Atypical?

To understand what makes a B cell “atypical,” it helps to first consider the job of a conventional B cell. When a B cell encounters a foreign substance, it can mature into either a plasma cell or a memory cell. Plasma cells produce large quantities of antibodies to fight an active infection. Memory cells persist long after the infection is gone, providing long-term immunity if the same invader returns.

Atypical B cells (ABCs) deviate from this standard path. Their identity is defined by a unique set of biological markers on their surface, such as the protein CD11c. Internally, these cells often express a transcription factor known as T-bet, which directs the cell’s development and function. This combination of markers is uncommon on conventional B cells.

Functionally, atypical B cells are also different. They are less effective at multiplying and turning into antibody-producing plasma cells when stimulated. This has led researchers to consider them “exhausted,” a term for cells overstimulated to the point of reduced function. The antibodies they produce may also be of lower quality than those from a classic immune response.

“Atypical” does not mean “cancerous.” Cancer involves uncontrolled cell growth, which is not a feature of atypical B cells. These are non-malignant cells that arise from a specific immune reaction, often in response to prolonged inflammation, and follow an alternative developmental pathway.

Why Do Atypical B Cells Appear?

The emergence of atypical B cells is a direct consequence of the immune system being in a state of high, sustained alert. When the body faces a persistent threat it cannot easily clear, the resulting chronic activation provides the conditions for ABCs to develop. Researchers have identified several scenarios where this prolonged immune stimulation occurs.

One well-studied trigger is chronic infection. Pathogens the body struggles to eliminate, such as HIV, hepatitis C, and malaria parasites, place the immune system under lasting stress. The constant presence of the infectious agent drives the generation of atypical B cells. For example, studies in malaria-exposed individuals show a significant expansion of ABCs, sometimes constituting over half of all circulating B cells.

Autoimmune diseases are another driver of ABC formation. In conditions like systemic lupus erythematosus (SLE) and rheumatoid arthritis, the immune system mistakenly attacks the body’s own tissues. This creates chronic inflammation and immune activation similar to a long-term infection. Individuals with these diseases often have elevated numbers of atypical B cells, which are thought to play an active role in the disease.

The process of aging also contributes to their appearance. As people get older, their immune systems undergo changes known as immunosenescence, which includes a gradual increase in low-grade, chronic inflammation. This age-related inflammatory state promotes the development of atypical B cells. Older individuals tend to have higher numbers of these cells compared to younger people, even without a specific infection or autoimmune condition.

The Impact of Atypical B Cells on Health

A large population of atypical B cells has tangible consequences for health. These cells are associated with a dysregulated immune response, contributing to both weakened defenses and autoimmune-driven damage. Their accumulation is a sign that the immune system is struggling to maintain balance.

One health impact is impaired vaccine responses. Because many atypical B cells are “exhausted,” they do not respond effectively to stimulation from vaccines, leading to weaker protection. For instance, studies have shown that a higher number of ABCs is associated with a poorer antibody response to the influenza vaccine. This undermines the goal of vaccination, leaving individuals more vulnerable.

In autoimmune diseases like lupus, atypical B cells are a primary source of harmful autoantibodies that attack the body’s tissues. In this setting, the antibodies they generate target the self, causing inflammation and damage to organs like the kidneys, skin, and joints. The expansion of ABCs in lupus is not just a symptom but a direct contributor to its progression.

In chronic infections like HIV, a high frequency of atypical B cells is a marker of an immune system becoming worn out. These cells are less capable of producing effective antibodies to control the virus long-term. Their presence indicates the immune system is shifting toward a less functional state, affecting its ability to manage the infection and defend against other pathogens.

The involvement of atypical B cells in disease has made them a target for new medical therapies. Researchers are exploring ways to eliminate or modify these cells to restore proper immune function. Targeting the cells that drive autoimmunity or signify immune exhaustion may lead to more effective treatments for conditions where ABCs play a damaging role.