Control of B-1a cell development by instructive BCR signaling

Kreslavsky, Taras; Wong, Jeffrey J.; Fischer, Maria; Skok, Jane A.; Busslinger, Meinrad

doi:10.1016/j.coi.2018.01.001

Cited by 30 publications

(22 citation statements)

References 70 publications

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“…Immune cells are generated by hematopoietic stem and precursor cells (HSPCs). In the mouse model, evidence has been obtained for the developmentally ordered appearance (or “layered development”) of distinct HSPCs that give rise to distinct immune cell lineages at different stages of development, including the generation of innate lymphocytes such as dendritic epidermal T cells and B1 lymphocytes (Ikuta et al, 1990; Havran and Allison, 1990; Yuan et al, 2012; Ginhoux and Jung, 2014; Beaudin et al, 2016; Ramond et al, 2014; Gentek et al, 2018; Kreslavsky et al, 2018; Smith et al, 2018). However, other studies indicate that the available niche at the time of development is more important (van de Laar et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

The human fetal thymus generates invariant effector γδ T cells

Tieppo

Papadopoulou

Gatti

et al. 2019

Journal of Experimental Medicine

137

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In the mouse thymus, invariant γδ T cells are generated at well-defined times during development and acquire effector functions before exiting the thymus. However, whether such thymic programming and age-dependent generation of invariant γδ T cells occur in humans is not known. Here we found that, unlike postnatal γδ thymocytes, human fetal γδ thymocytes were functionally programmed (e.g., IFNγ, granzymes) and expressed low levels of terminal deoxynucleotidyl transferase (TdT). This low level of TdT resulted in a low number of N nucleotide insertions in the complementarity-determining region-3 (CDR3) of their TCR repertoire, allowing the usage of short homology repeats within the germline-encoded VDJ segments to generate invariant/public cytomegalovirus-reactive CDR3 sequences (TRGV8-TRJP1-CATWDTTGWFKIF, TRDV2-TRDD3-CACDTGGY, and TRDV1-TRDD3-CALGELGD). Furthermore, both the generation of invariant TCRs and the intrathymic acquisition of effector functions were due to an intrinsic property of fetal hematopoietic stem and precursor cells (HSPCs) caused by high expression of the RNA-binding protein Lin28b. In conclusion, our data indicate that the human fetal thymus generates, in an HSPC/Lin28b-dependent manner, invariant γδ T cells with programmed effector functions.

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Section: Introductionmentioning

confidence: 99%

The human fetal thymus generates invariant effector γδ T cells

Tieppo

Papadopoulou

Gatti

et al. 2019

Journal of Experimental Medicine

137

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“…B-1 cells display a primitive, innate-like functionality and produce natural antibodies, independent of T cell help (Hayakawa et al, 1983). In humans, the existence of a B-1 cell counterpart is debated (Baumgarth, 2011;Caligaris-Cappio et al, 1982;Ehrhardt et al, 2005;Griffin et al, 2011;Kreslavsky et al, 2018;Kruetzmann et al, 2003;Perez-Andres et al, 2011;Rakhmanov et al, 2009;Reynaud and Weill, 2012;Wardemann et al, 2002;Weller et al, 2008), CD5 expression is not confined to a fetal B cell lineage (DiLillo et al, 2010;Seifert et al, 2012;Sims et al, 2005;Wortis et al, 1995) and human neonatal B cells share only few of the defects observed in mice (Adkins et al, 2004;Tasker and Marshall-Clarke, 2003).…”

Section: Introductionmentioning

confidence: 99%

Human neonatal B cell immunity differs from the adult version by conserved Ig repertoires and rapid, but transient response dynamics

Budeus

Kibler

Brauser

et al. 2020

Preprint

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SUMMARYThe human infant B cell system is considered premature or impaired. Here we show that neonates have mature and fully functional B cell subsets as seen in adults, albeit with distinct transcriptional programs providing accelerated responsiveness to T cell independent and T cell dependent stimulation and facilitated IgA class switching. Stimulation drives extensive differentiation into antibody secreting cells, thereby presumably limiting memory B cell formation. The neonatal Ig-repertoire is highly variable, but conserved, showing 8% recurrent B cell receptor (BCR) clonotypes shared between neonates. Our study demonstrates that neonatal B cells are neither premature nor impaired, but differ from their adult counterpart in a conserved BCR repertoire and rapid but transient response dynamics. These properties may account for the sensitivity of neonates to infections and limited effectivity of vaccination strategies. Finally, our findings have implications for a limited comparability of mouse models to human infant B cell immunity.

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“…In the case of B1 cells, this possibly even occurs prior to hematopoietic stem cell differentiation (7)(8)(9)(10). As recently reviewed in detail, definitive evidence for the lineage model is still lacking, with both putative BCR-negative B1 progenitors and exclusive progenitor commitment to B2 differentiation being controversial (11,12). In the "selection model," B cell progenitors are instructed by BCR specificity to differentiate into B1 cells, depending on BCR-mediated recognition of common bacterial and certain self antigens (2,13).…”

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confidence: 99%

BCR-dependent lineage plasticity in mature B cells

Graf

Seagal

Otipoby

et al. 2019

Science

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B2 cells engage in classical antibody responses, whereas B1 cells are considered carriers of innate immunity, biased toward recognizing epitopes present on the surfaces of common pathogens and self antigens. To explore the role of B cell antigen receptor (BCR) specificity in driving B1 cell differentiation, we developed a transgenic system allowing us to change BCR specificity in B cells in an inducible and programmed manner. Mature B2 cells differentiated into bona fide B1 cells upon acquisition of a B1 cell–typical self-reactive BCR through a phase of proliferative expansion. Thus, B2 cells have B1 cell differentiation potential in addition to their classical capacity to differentiate into memory and plasma cells, and B1 differentiation can be instructed by BCR-mediated self-reactivity, in the absence of B1-lineage precommitment.

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Control of B-1a cell development by instructive BCR signaling

Cited by 30 publications

References 70 publications

The human fetal thymus generates invariant effector γδ T cells

The human fetal thymus generates invariant effector γδ T cells

Human neonatal B cell immunity differs from the adult version by conserved Ig repertoires and rapid, but transient response dynamics

BCR-dependent lineage plasticity in mature B cells

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