Multifaceted B-cell response to transient HIV viraemia in elite controllers

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 28, 2024

ABSTRACT Chronic HIV infection drives B-cell dysfunction associated with the accumulation of tissue-like memory (TLMs) and activated B cells (MBCs) but decline in resting cells. TLMs express multiple inhibitory receptors lack response to soluble antigens. However, their origin mechanisms driving expansion remain unclear. By using bulk BCR sequencing cell subsets from elite controllers an ART-controlled cohort, we revealed that (CD21 - CD27 cells) were significantly less mutated also diverse than other MBCs, suggesting enrichment for innate-like or they belong a mature subset. Subsequent detailed multi-omics study immune controller transient viraemia demonstrated functional increase Env-reactive IgG MBCs non-TLM phenotype. Single-cell RNA/BCR PMBCs enriched orchestrated TNF-alpha followed by interferon alpha gamma across all subsets. We noted emergence extrafollicular PLD4+ plasmablasts previously undepreciated heterogeneity stable TLM population. identified two distinct subsets: TLM1 (T-bet low ) TLM2 hi differed differentiation stage, isotype use mutational burden. Surprisingly, both (TLM1 more TLM2) IGHV4-34 segment (associated self-reactivity) displayed persistent activation signalling signature, indicating (with indices) strong presence pseudotime analyses contained not only conventional lineages, further highlighting complexity whole compartment. This provides new insight into multifaceted as likely happens during early phase anti-retroviral therapy cessation, contribution which might have important clinical implications anti-HIV vaccine design.

Язык: Английский

Polarization of the memory B cell response

Journal of Leukocyte Biology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 14, 2024

Abstract Memory B cells are long-lived that induced following infection or vaccination. Upon antigen re-encounter, memory rapidly differentiate into antibody-secreting germinal center cells. While an important component of long-term protective immunity vaccination, they also contribute to the progression diseases such as autoimmunity and allergy. Numerous subsets have been identified in mice humans possess phenotypic functional differences. Here, we review transcriptional circuitry governing B-cell differentiation function. We then summarize emerging evidence inflammatory environment which develop has role shaping their phenotype examine pathways regulating development during a type 1-skewed 2-skewed immune response.

Язык: Английский