Role of B1 Cells in SLE Is Better Understood, but Questions Remain

B cells are known to play a role in systemic lupus erythematosus (SLE), but the role of B1 cells, a type of B cell, has yet to be fully understood.

In a new review article, investigators outlined the latest research and findings related to B1 cells and SLE. They wrote that the evidence suggests B1 cells play a role in the development of SLE, but the cells’ specific functions in the disease require more investigation. Their findings were published in Frontiers in Immunology.

They began by explaining why B cells are an important area of study in SLE. The disease involves dysfunction of the immune system, including an overactivation of T cells and B cells and overproduction of autoantibodies. Antibody-producing B cells have been a meaningful target for therapies such as rituximab (Rituxan) and belimumab (Benlysta), the authors noted.

However, B1 cells pose a particular problem for B1-antagonist therapies.

“B1 cells are a group of B cells that are colonized in the peritoneum and pleural cavities, which enables them to evade drugs,” the authors wrote. “Moreover, the growth and development of B1 cells do not depend on the B-cell activation factor; thus, drugs that target B cells are ineffective.”

In reviewing the latest knowledge about B1 cells, the investigators explained the findings of recent research in 2 settings: in mouse models of SLE and humans with SLE.

In mouse models, B1 cells have been shown to generate both natural immunoglobulin M (nIgM) and immunoglobulin G antibodies, the latter of which may be associated with elevated production of recombination activating genes (RAGs) in mice. Previous research has suggested that the number of B1 cells with high RAG expression is an indicator of disease activity.

B1 cells also appear to stimulate the proliferation of CD4+ T cells and the cells’ differentiation toward proinflammatory Th1 and Th17 cells, the authors said, which is a mechanism that promotes SLE. Other research indicates that B1 cells contribute to organ damage, because in SLE they can accumulate in various inflammatory regions.

“By migrating to the inflamed organ, B1 cells that were originally confined to the peritoneal cavity are able to communicate with numerous other immune cells, exert their antigen-presenting cell capacity, stimulate the proliferation and differentiation of T cells, and switch to a proinflammatory phenotype,” the authors explained.

Lastly, the investigators noted the B1 cells secrete immune-regulating cytokines, such as interleukin 10, which appears to influence the disease in multiple ways.

Turning to the evidence from human patients with SLE, the authors noted that nIgM is produced by B1 cells and “acts as a first line of immune defense,” including by offering protection against cardiovascular disease. Yet, when B1 cells are altered in patients with SLE, the cells produce less IgM.

As with mice, early research in humans similarly suggests that B1 cells stimulate CD4+ T cells.

The study authors said B cells, B1 cells, and B2 and Breg cells all continue to be important areas of ongoing study.

“Although several studies have revealed that B1 cells are involved in the development of SLE by secreting antibodies, activating T cells, producing cytokines, and migrating to target organs, their specific role in human autoimmune diseases requires further exploration,” the authors concluded.

Specific questions to be addressed include how the B-cell phenotype can be determined in humans and how B1 cells self-regulate their proliferation and secretion, they said.

Reference

She Z, Li C, Wu F, et al. The role of B1 cells in systemic lupus erythematosus. Front Immunol. Published online March 28, 2022. doi:10.3389/fimmu.2022.814857