Table 3.

Cells of the adaptive immune system in TME: B cell subpopulations.

Cell Type	Marker	Production	Function	Reference
B cells	CD19+ CD20+	various cytokines	B cells are essential players of humoral immunity through antibody (Ab) production. They recognize antigens by the B cell receptor (BCR) composed of membrane-bound antibody. B cells are divided into (1) B1 B cells, mainly found in the peritoneal and pleural cavities; (2) B2 or FO B cells, which are located in lymph nodes; and (3) marginal zone B cells, which are in the marginal sinus of the spleen. The different subsets are activated in a T cell-dependent or -independent way. Reactive conditions: B cell activation begins when the B cell binds to an antigen via its BCR. This activation causes proliferation and differentiation into plasma B cells (PCs), which produce and release antibodies. Malignant conditions: B cells can be implicated in the presentation of tumor-specific antigens to T cells, the production of tumor-specific antibodies and immune regulation as Bregs.	[1,6]
Ab-producing B cells	CD19+ CD20+	tumor-specific IgG and IgA	Reactive conditions: B cells can secrete Abs, and thereby start a specific immune response in viral and/or bacterial infections and autoimmune diseases. Malignant conditions: B cell-mediated Ab production can lead to the killing of tumor cells through the complement cascade activation, phagocytosis by macrophages, and activation of tumor-killing activity of NK cells.	[1,6]
B cells as APCs	CD19+ CD20+ CD21+ CD23+ CD27− IgG1+ CD40+ CD80+ CD86+ MHC class II+	IL-2 IL-6 CCL3 CCL4 ICAM1 GM-CSF	Reactive conditions: B cells can recognize antigen in inflammatory processes in a T cell-independent manner, and they possess the function to present these antigens via their MHC class II surface molecule and thus induce T cell responses. Malignant conditions: B cells can be found nearby T cells in several types of cancers, including when DCs are absent. These cells act as APCs to CD4+ T cells. There exist two forms of this type of cell, causing either anti-tumor immune responses or immunosuppressive intratumoral conditions: (1) the activated B cells (CD69+, HLA-DR+, CD27+, CD21+), possessing Th1 T cell activating function (anti-tumor immune responses); and (3) the exhausted B cells (CD69+, HLA-DR+, CD27−, CD21−), leading to the generation of Tregs (immunosuppressive condition).	[1,6]
Bregs	CD19+ CD21+ CD24+ CD25+ FOXP3+	IL-10 IL-35 TGF-β	Reactive conditions: Bregs are mainly implicated in mediating immune tolerance in autoimmune diseases, including systemic lupus erythematosus (SLE) and multiple sclerosis. Malignant conditions: Bregs possess a tumor-promoting function. They can suppress CD4+ T cell proliferation and induce forkhead box P3 (FOXP3) expression in Tregs mediated by IL-10 and TGF-β. Bregs can also suppress CD8+ T cells in their effector function by IL-10. Furthermore, they cause immune inhibitory receptors PD-L1 on cancer cells through IL-10, IL-35, and TGF-β secretion.	[1,6]