B-cell

B-cell

Overview

B cells (B lymphocytes) are a critical subset of adaptive immune cells originating from hematopoietic stem cells in the bone marrow, where they undergo sequential developmental stages before being released into peripheral circulation as mature, naïve lymphocytes. Their defining feature is the expression of a unique B-cell receptor (BCR) — a membrane-bound immunoglobulin capable of recognizing specific antigens — alongside surface markers including CD19, CD20 (MS4A1), and MHC class II molecules. Upon antigen encounter, particularly in the context of T-cell help within germinal centers, B cells undergo clonal expansion, somatic hypermutation, and class-switch recombination, ultimately differentiating into antibody-secreting plasma cells or long-lived memory B cells. Beyond antibody production, B cells serve as professional antigen-presenting cells (APCs), processing and presenting peptide-MHC class II complexes to CD4+ T cells, thereby actively shaping the broader adaptive immune landscape.

B cells are central to humoral immunity and occupy a pivotal position at the intersection of protective immunity, autoimmunity, and cancer immunosurveillance. Dysregulation of B-cell development, activation, or tolerance checkpoints underlies a spectrum of diseases ranging from hematologic malignancies and autoimmune conditions such as diabetes and multiple sclerosis, to impaired responses in infection and transplantation settings. The capacity of B cells to be engineered, depleted, or redirected therapeutically — through monoclonal antibodies, gene editing, nanoparticle platforms, and adoptive cell strategies — has made them a major focus of contemporary immunological and oncological research.


Focus of Latest Publications

Recent publications have focused on B cells as central participants in anti-tumor immunity, vaccine responses, autoimmunity, and hematopoietic reconstitution. In breast cancer samples after neoadjuvant therapy, spatial multi-omics showed that B cells are nearest neighbors of Tpex cells within tertiary lymphoid structures and may promote Tpex invigoration through ICOSL-ICOS and CD86-CD28 interactions. A related multiomic study in resectable non-small cell lung cancer examined B cells and tertiary lymphoid structures in the setting of perioperative chemoimmunotherapy to characterize immune features associated with complete pathologic response. Together, these studies highlight B cells as key components of therapy-associated immune niches.

Several reports addressed B-cell function in antigen presentation and humoral immunity. Multivalent nanoparticle vaccines were shown to engage antigen-specific B cells as antigen-presenting cells for CD4+ T cell priming, with B cells and dendritic cells acting redundantly to initiate early T cell activation; B cells alone were sufficient to drive naive CD4+ T cell proliferation when MHC class II was absent on non-B cells. Another study used highly multiplexed DNA-tagged SARS-CoV-2 antigen panels to sort thousands of antigen-binding circulating B cells and found that atypical B cells and a subset of class-switched memory cells were enriched for antigen binding, while post-germinal center B cells showed increasing variant-binding breadth and somatic hypermutation over time. Vaccination, compared with infection, preferentially stimulated B cells expressing antibodies with inherently high antigen-binding breadth.

B cells were also investigated in therapeutic engineering and immune modulation. Hematopoietic stem and progenitor cell gene editing was used to generate edited B lymphocytes that, after antigen activation, expanded and differentiated into plasma cells producing long-lasting therapeutic antibodies or cargo proteins, including antibodies against HIV type 1, malaria, and influenza A virus. In a lymph node-targeted nano-prodrug strategy for collagen-induced arthritis, localized delivery of ibrutinib with Hyaluronan sodium was used to modulate B-cell responses; the treatment inhibited antigen-presenting B cells and germinal center activity and reduced joint inflammation in mice. In experimental autoimmune encephalomyelitis, B cells were reported to regulate disease transfer in a model showing that an adaptive cellular source of IL-17A and IL-17F is critical for disease induction.

Other studies examined B-cell development and reconstitution in disease settings. In Alzheimer’s disease, immune cell-specific multi-omics identified B-cell-associated genes among candidate risk loci with cell-type-specific associations. In a patient with X-linked lymphoproliferative disease after hematopoietic stem cell transplant, an acquired nonpermissive bone marrow microenvironment impaired B-cell development, with a block at the pre-BI stage linked to reduced CXCL12 production by mesenchymal stromal cells and defective support for B-cell development.

Key Publications

  • NEWJun Spatial multi-omics implicate the interaction between Tpex and B cells in tertiary lymphoid structures after neoadjuvant therapy. (Cancer discovery, 2026, PMID 42339989): "B cells are nearest neighbors of Tpex cells in TLSs and B cells promote invigoration of Tpex cells via ICOSL-ICOS and CD86-CD28 interactions within TLSs."
  • NEWJun Immune cell-specific genetic architecture of Alzheimer's disease revealed by multi-omics analysis for therapeutic target discovery and prioritization. (Translational psychiatry, 2026, PMID 42331779): "Notable candidates included GATS, HLA-DOB, HLA-DQA1, PM20D1, and others, with each gene demonstrating a cell-type-specific association restricted to its corresponding immune cell type, such as monocytes, CD8 + T cells, or B cells."
  • May Multivalent nanoparticles activate T-dependent antibody response via antigen presentation by both B cells and dendritic cells. (Cell reports, 2026, PMID 42085184): "Moreover, B cell-mediated antigen presentation was required for inducing TD responses beyond the draining lymph nodes."
  • Apr An adaptive cellular source of IL-17A and IL-17F is critical for the induction of experimental autoimmune encephalomyelitis. (Science immunology, 2026, PMID 42030372): "We further show that B cells can regulate the transfer of EAE disease in this context."
  • Apr B lymphocyte protein factories produced by hematopoietic stem cell gene editing. (Science (New York, N.Y.), 2026, PMID 41990179): "In mice, edited B lymphocytes derived from transplanted HSPCs were activated by cognate antigen, underwent clonal expansion, and developed into specific antibody-synthesizing or cargo protein-synthesizing plasma cells."
  • May Multiplexed antigen panel analysis identifies B cell phenotype and receptor genetic contributions to antibody breadth. (Immunity, 2026, PMID 41928519): "Atypical B cells and a subset of class-switched memory cells with evidence of recent germinal center exposure were enriched for antigen binding."
  • Apr Decoding B-cell Signatures of Complete Pathologic Response to Perioperative Chemoimmunotherapy in Non-Small Cell Lung Cancer. (Clinical cancer research : an official journal of the American Association for Cancer Research, 2026, PMID 41805895): "We provide a multiomic characterization of B cells and tertiary lymphoid structures (TLS) to dissect the immune landscape associated with CPR."
  • Feb Lymph nodes-targeted nano-prodrug for precise B cell immunoregulation to prevent collagen-induced arthritis. (Biomaterials, 2026, PMID 41687284): "HC-IBR plus laser exhibited better efficiency in inhibition of antigen-presenting B cell and germinal center to control the development of joint inflammation in mice with collagen induced arthritis."
  • Apr Acquired nonpermissive BM microenvironment impairs HSC proliferation and maintenance, and B-cell development after HSCT. (Blood advances, 2026, PMID 41544216): "Defects in B-cell reconstitution upon hematopoietic stem cell (HSC) transplant (HSCT) are a common observation, yet the mechanism remains unexplained."