Revealing the role of regulatory b cells in cancer: development, function and treatment significance

Abstract

B cells are essential components of the immune response, primarily recognized for their ability to produce antibodies. However, emerging research reveals their important roles in regulating immune responses and influencing tumor development, independent of antibodies. The connection between tumor progression and alterations in the tumor microenvironment is well-established, as immune infiltrating cells can enhance the survival of tumor cells by modifying their surroundings. Despite this, the majority of studies have focused on T cells and macrophages, creating a gap in our understanding of B cells. Regulatory B cells (Bregs) represent a crucial subpopulation that plays a significant role in maintaining immune balance. They may have a substantial impact on tumor immunity by negatively regulating tumor-infiltrating immune cells. This paper reviews the existing literature on Bregs, examining their development, phenotypes, functions, and the mechanisms through which they exert their regulatory effects. Furthermore, we highlight their potential interventional roles and prognostic significance in cancer therapy. By addressing the current gaps in knowledge regarding Bregs within tumors, we hope to inspire further research that could lead to innovative cancer treatments and improved outcomes for patients.

Keywords: Breg cells; Breg development; Breg function; Breg subtypes; Cancer prognosis.

Fig. 1

Growth and development of Bregs. Common lymphoid progenitor (CLP) cells develop into immature cells in bone marrow, and then enter in the circulation, through transitional B cells, separate marginal zone (MZ) B cells and follicular (FO) B cells, and finally become mature B cells. Immature B cells could develop into Bregs with the stimulation of TLR ligands, while mature B cells can also be turned into Bregs by adequate stimulation

Fig. 2

Functions of Bregs. Breg, which is transformed from B cells under different stimuli, on the one hand promotes the transformation of naive CD4⁺T cells into Tr1 and Treg cells to assist iNKT; On the other hand, it prevents the differentiation of Th17 cells and the Th1 cell response, and inhibits macrophage and DC cells functions. In addition, Bregs also participates in the process of apoptosis