The flawless immune tolerance of pregnancy

International audienc

Un exemple de tolérance: l'immunologie de la grossesse

National audienceLa grossesse est longtemps restée un mystère aux yeux des immunologistes : comment concilier le fait qu’une mère soit capable de tolérer son fœtus, par définition incompatible sur le plan immunologique, alors qu’elle rejette une greffe allogénique ? Les études récentes sur l’immunologie de la grossesse ont permis de lever au moins partiellement le voile sur les nombreux mécanismes mis en place en contexte gestationnel pour permettre cette tolérance sélective et temporaire. Toutes les étapes de l’alloreconnaissance T font ainsi l’objet d’une régulation, protégeant le fœtus d’une réaction délétère. Certains acteurs impliqués sont doués de mémoire, ce qui faciliterait le déroulement de grossesses ultérieures issues d’un même père. À noter que le défaut de ces phénomènes actifs peut conduire à des pathologies obstétricales telles que la prééclampsie ou les fausses couches

[Perspectives for the evolution and use of CAR-T cells]

National audienceCAR-T cells have recently made a stunning entry on the arena of immunotherapy of B-cell lymphomas. This new treatment approach represents the culmination of 30 years of efforts to understand the role of T cells in the antitumor response. However, this technology is still in its infancy and suffers from a number of limitations. Many areas for improvement, based in particular on the possibilities of additional genetic manipulations of CAR-T cells, aim at reducing their toxicity, increasing their persistence in vivo, preventing the risk of tumor escape, recruiting other immune effectors, or extending their application to other cancers. Further studies of the dynamic interaction between the patient and these live drugs will allow elucidating the mechanisms determining the antitumor response in this context and thus developing more efficiently the future CAR-T cells

Characterization of the novel HLA‐DQA1 *05:18 allele by next‐generation sequencing

International audienc

Characterization of the novel HLA‐DQA1 *01:19 allele by next‐generation sequencing

International audienc

Characterization of the novel HLA‐DQA1 *01:39 allele by next‐generation sequencing

International audienc

NGFR regulates stromal cell activation in germinal centers

International audienceNerve growth factor receptor (NGFR) is expressed by follicular dendritic cells (FDCs). However, the role of NGFR in the humoral response is not well defined. Here, we study the effect of Ngfr loss on lymph node organization and function, demonstrating that Ngfr depletion leads to spontaneous germinal center (GC) formation and an expansion of the GC B cell compartment. In accordance with this effect, stromal cells are altered in Ngfr(-/-) mice with a higher frequency of FDCs, characterized by CD21/35, MAdCAM-1, and VCAM-1 overexpression. GCs are located ectopically in Ngfr(-/-) mice, with lost polarization together with impaired high-affinity antibody production and an increase in circulating autoantibodies. We observe higher levels of autoantibodies in Bcl2 Tg/Ngfr(-/-) mice, concomitant with a higher incidence of autoimmunity and lower overall survival. Our work shows that NGFR is involved in maintaining GC structure and function, participating in GC activation, antibody production, and immune tolerance

Demultiplexing Ig repertoires by parallel mRNA/DNA sequencing shows major differential alterations in severe COVID-19

To understand the fine differential elements that can lead to or prevent acute respiratory distress syndrome (ARDS) in COVID-19 patients, it is crucial to investigate the immune response architecture. We herein dissected the multiple layers of B cell responses by flow cytometry and Ig repertoire analysis from acute phase to recovery. Flow cytometry with FlowSOM analysis showed major changes associated with COVID-19 inflammation such as an increase of double-negative B-cells and ongoing plasma cell differentiation. This paralleled COVID-19-driven expansion of two disconnected B-cell repertoires. Demultiplexing successive DNA and RNA Ig repertoire patterns characterized an early expansion of IgG1 clonotypes with atypically long and uncharged CDR3, the abundance of this inflammatory repertoire being correlated with ARDS and likely pejorative. A superimposed convergent response included convergent anti-SARS-CoV-2 clonotypes. It featured progressively increasing somatic hypermutation together with normal-length or short CDR3 and it persisted until a quiescent memory B-cell stage after recovery