B Cells in Breast Cancer Pathology

Abstract

B cells have recently become a focus in breast cancer pathology due to their influence on tumour regression, prognosis, and response to treatment, besides their contribution to antigen presentation, immunoglobulin production, and regulation of adaptive responses. As our understanding of diverse B cell subsets in eliciting both pro- and anti-inflammatory responses in breast cancer patients increases, it has become pertinent to address the molecular and clinical relevance of these immune cell populations within the tumour microenvironment (TME). At the primary tumour site, B cells are either found spatially dispersed or aggregated in so-called tertiary lymphoid structures (TLS). In axillary lymph nodes (LNs), B cell populations, amongst a plethora of activities, undergo germinal centre reactions to ensure humoral immunity. With the recent approval for the addition of immunotherapeutic drugs as a treatment option in the early and metastatic settings for triple-negative breast cancer (TNBC) patients, B cell populations or TLS may resemble valuable biomarkers for immunotherapy responses in certain breast cancer subgroups. New technologies such as spatially defined sequencing techniques, multiplex imaging, and digital technologies have further deciphered the diversity of B cells and the morphological structures in which they appear in the tumour and LNs. Thus, in this review, we comprehensively summarise the current knowledge of B cells in breast cancer. In addition, we provide a user-friendly single-cell RNA-sequencing platform, called "B singLe cEll rna-Seq browSer" (BLESS) platform, with a focus on the B cells in breast cancer patients to interrogate the latest publicly available single-cell RNA-sequencing data collected from diverse breast cancer studies. Finally, we explore their clinical relevance as biomarkers or molecular targets for future interventions.

Keywords: B cells; breast cancer; germinal centres; lymph nodes; tertiary lymphoid structures; tumour-infiltrating lymphocytes.

Figure 1

B cell development and differentiation. B cells primarily originate from CD34+CD19− haematopoietic stem cells within the bone marrow, where rearrangement of immunoglobulin heavy and light chains through V(D)J recombination leads to the development of functional IgM+ immature B cells. Those that survive tolerance checks to prevent autoreactivity migrate through the bloodstream or lymphatics to secondary lymphoid organs. Following exposure to cognate antigen, mature B cells can undergo plasmacytic differentiation to generate short-lived plasma cells or establish a germinal centre reaction. Within the germinal centre, B cells undergo iterative rounds of somatic hypermutation and selection through interactions with follicular T helper (Tfh) and follicular dendritic cells (FDC). The resultant B cell pool will exit the germinal centre as high-affinity memory B or plasma cells.

Figure 2

Histological identification of TLS and germinal centres within tumour and LN. The top row displays images of a primary breast tumour with TLS stained with: H&E, CD20, CD27, CD138, and merge of CD20 (red), CD27 (green), and CD138 (magenta). Dense CD20+ B cell areas of the TLS are surrounded by CD27+ cells and dispersed plasma cells. Yellow arrows indicate TLS. The bottom row shows a metastatic LN from the same patient exhibiting germinal centre formation, stained with: H&E, CD20, CD27, CD138, and merge of CD20 (red), CD27 (green) and CD138 (magenta). Yellow arrows indicate germinal centres.