The expansion of human T-bethighCD21low B cells is T cell dependent.

Accumulation of human CD21low B cells in peripheral blood is a hallmark of chronic activation of the adaptive immune system in certain infections and autoimmune disorders. The molecular pathways underpinning the development, function, and fate of these CD21low B cells remain incompletely characterized. Here, combined transcriptomic and chromatin accessibility analyses supported a prominent role for the transcription factor T-bet in the transcriptional regulation of these T-bethighCD21low B cells. Investigating essential signals for generating these cells in vitro established that B cell receptor (BCR)/interferon-γ receptor (IFNγR) costimulation induced the highest levels of T-bet expression and enabled their differentiation during cell cultures with Toll-like receptor (TLR) ligand or CD40L/interleukin-21 (IL-21) stimulation. Low proportions of CD21low B cells in peripheral blood from patients with defined inborn errors of immunity (IEI), because of mutations affecting canonical NF-κB, CD40, and IL-21 receptor or IL-12/IFNγ/IFNγ receptor/signal transducer and activator of transcription 1 (STAT1) signaling, substantiated the essential roles of BCR- and certain T cell­derived signals in the in vivo expansion of T-bethighCD21low B cells. Disturbed TLR signaling due to MyD88 or IRAK4 deficiency was not associated with reduced CD21low B cell proportions. The expansion of human T-bethighCD21low B cells correlated with an expansion of circulating T follicular helper 1 (cTfh1) and T peripheral helper (Tph) cells, identifying potential sources of CD40L, IL-21, and IFNγ signals. Thus, we identified important pathways to target autoreactive T-bethighCD21low B cells in human autoimmune conditions, where these cells are linked to pathogenesis and disease progression.

Linfocitos NKT invariantes: ontogenia, fenotipo y función / Invariant NKT lymphocytes: ontogeny, phenotype and function

Las células NKT invariantes (NKTi) fueron identificadas inicialmente por presentar características similares a las célulasT y NK. Actualmente se han definido como linfocitosT con características únicas, desde su selección y diferenciación en el timo hasta su respuesta a estímulos específicos. A partir de estudios realizados en ratones se han caracterizado las vías de maduración y diferenciación de esta población celular, en las cuales la molécula CD1d, tiene un papel fundamental en la selección de sus precursores y, adicionalmente, en la presentación de glucolipídicos para la activación de las células NKTi en periferia. En sangre periférica humana se han encontrado 4subpoblaciones de células NKTi: CD4+, CD8αβ+, CD8αα+ y Doble Negativas, las cuales cooperan e interactúan de forma particular con las demás células del sistema inmune. Finalmente, estudios de las células NKTi muestran la posibilidad de plantear alternativas terapéuticas, pero a su vez abren más interrogantes sobre el comportamiento de este tipo de linfocitos

Invariant natural killer (iNK) T lymphocytes (iNKTL) were initially identified due to having similar characteristics to NK and Tcells. Nowadays, it is known that these cells are Tlymphocytes with unique characteristics, from their maturing process and differentia tion in the thymus to the response at specific stimuli. Studies in mice have been useful for examining the maturing process and differentiation pathways of iNKTL. In these pathways the CD1d molecule has a fundamental role in the selection of their precursors, and also in the peripheral glycolipid presentation for the activation of iNKTL. Four sub-populations of iNKTL CD4+, CD8+, CD8+ and Double Negatives, were identified in human peripheral blood. They particularly cooperate and interact with others immune cells. The information obtained by studying iNKTL opens the possibility of proposing this cell line as a therapeutic alternative, but further studies on the behavior of this type of lymphocyte are needed