Role of CD11c + T-bet + B cells in human health and disease

Abstract

A growing body of evidence suggests that when B cells are chronically stimulated, a phenotypically unique subset expands. Data suggest that this atypical population contains B cell receptor (BCR) specificities capable of binding the antigen, or sets of antigens that initiated the expansion of these cells. These B cells have been given various names, including double negative B cells, atypical memory B cells, tissue-like memory B cells, or age associated B cells (ABCs). However, on close inspection these reports described B cell subsets that closely resemble B cells we refer to as CD11c B cells that often express T-bet. Here we will review the human studies that describe atypical memory B cells and compare and contrast their phenotype and suggested function in health and disease.

Innate-like B cell subsets during immune responses: Beyond antibody production

“…100,106,108,109 ABCs innate-like nature is exemplified by poor responsiveness to BCR and CD40 ligation, despite they possess IgM surface-levels comparable to those seen in conventional FO B cells; instead, they efficiently respond to TLR7 and TLR9 ligation, both innate receptors that synergize with BCR signaling to induce stronger proliferation outcomes. 100 ABCs mainly secrete Igs after TLRs (but not BCR only) stimulation 103,110 ; thus being able to rapidly differentiate into Ab-secreting plasma cells preferentially switched to IgG2a or IgG2c classes. 101,105 They also have been described as robust producers of cytokines such as IL-10 and IFN-.…”

The immune cell landscape in kidneys of lupus nephritis patients

“…7, 2018; After acquisition, kidney biopsy samples were placed into HypoThermosol FRS preservation solution for 10-30 minutes on ice and then transferred to a cryovial containing 1 ml of CryoStor CS10 cryopreservation medium (BioLife Solutions). The cryovial was incubated on ice for [20][21][22][23][24][25][26][27][28][29][30] min and was then placed in a Mr. Frosty freezing container (Nalgene, #5100-0001) and transferred to a -80°C freezer overnight. Cryopreserved samples were then stored in liquid nitrogen and shipped on dry ice to the central processing site, where they were stored in liquid nitrogen until processing.…”

Exhaustion may not be in the human B cell vocabulary, at least not in malaria

“…[7][8][9] This subpopulation of MBCs, variously referred to as atypical MBCs, 10 tissue-like MBCs (TLMBCs) 11 or exhausted MBCs, 11 although not identical from infectious disease to infectious disease, have several features in common. is a large expansion of a subpopulation of MBCs that in healthy individuals represents only a small proportion of total B cells (approximately 3%-6%).…”

“…[7][8][9] However, at present it is not clear how atypical MBCs arise and whether they contribute to the inefficiency of antibody-mediated immunity in chronic infectious diseases. [7][8][9] However, at present it is not clear how atypical MBCs arise and whether they contribute to the inefficiency of antibody-mediated immunity in chronic infectious diseases.…”

“…is a large expansion of a subpopulation of MBCs that in healthy individuals represents only a small proportion of total B cells (approximately 3%-6%). [7][8][9] This subpopulation of MBCs, variously referred to as atypical MBCs, 10 tissue-like MBCs (TLMBCs) 11 or exhausted MBCs, 11 although not identical from infectious disease to infectious disease, have several features in common. They lack the classical marker for human MBCs, the TNF family member, CD27, and express low levels of the complement receptor, CD21, and show high expression of a variety of genes not expressed by classical MBCs including the T-cell transcription factor T-bet, that plays a critical role in T H1 fate commitment, the integrin CD11c generally expressed by dendritic cells (DCs).…”