Matches in SemOpenAlex for { <https://semopenalex.org/work/W4386741392> ?p ?o ?g. }
- W4386741392 abstract "Abstract HELLS/LSH (Helicase, Lymphoid Specific) is a SNF2-like chromatin remodelling protein involved in DNA methylation. Its loss-of-function in humans causes humoral immunodeficiency, called ICF4 syndrome (Immunodeficiency, Centromeric Instability, Facial anomalies). Here we show by our newly generated B-cell-specific Hells conditional knockout mouse model that HELLS plays a pivotal role in T-dependent B-cell responses. HELLS deficiency induces accelerated decay of germinal center (GC) B cells and impairs the generation of high affinity memory B cells and circulating antibodies. Mutant GC B cells undergo dramatic DNA hypomethylation and massive de-repression of evolutionary recent retrotransposons, which surprisingly does not directly affect their survival. Instead, they prematurely upregulate either memory B cell markers or the transcription factor ATF4, which is driving an mTORC1-dependent metabolic program typical of plasma cells. Treatment of wild type mice with a DNMT1-specific inhibitor phenocopies the accelerated kinetics, thus pointing towards DNA-methylation maintenance by HELLS being a crucial mechanism to fine-tune the GC transcriptional program and enable long-lasting humoral immunity." @default.
- W4386741392 created "2023-09-15" @default.
- W4386741392 creator A5012020181 @default.
- W4386741392 creator A5020736484 @default.
- W4386741392 creator A5020826079 @default.
- W4386741392 creator A5023634411 @default.
- W4386741392 creator A5026206327 @default.
- W4386741392 creator A5027108064 @default.
- W4386741392 creator A5037783700 @default.
- W4386741392 creator A5052856500 @default.
- W4386741392 creator A5087398679 @default.
- W4386741392 creator A5090741929 @default.
- W4386741392 creator A5092871253 @default.
- W4386741392 date "2023-09-14" @default.
- W4386741392 modified "2023-10-17" @default.
- W4386741392 title "Germinal center output is sustained by HELLS-dependent DNA-methylation-maintenance in B cells" @default.
- W4386741392 cites W1603729648 @default.
- W4386741392 cites W1652583010 @default.
- W4386741392 cites W1681312898 @default.
- W4386741392 cites W1953890763 @default.
- W4386741392 cites W1967841068 @default.
- W4386741392 cites W1970263046 @default.
- W4386741392 cites W1974058116 @default.
- W4386741392 cites W1976457281 @default.
- W4386741392 cites W1977099733 @default.
- W4386741392 cites W1981641790 @default.
- W4386741392 cites W1982905137 @default.
- W4386741392 cites W1985594917 @default.
- W4386741392 cites W1987318925 @default.
- W4386741392 cites W1988622164 @default.
- W4386741392 cites W1993833167 @default.
- W4386741392 cites W1997183854 @default.
- W4386741392 cites W2007080316 @default.
- W4386741392 cites W2012028187 @default.
- W4386741392 cites W2012955490 @default.
- W4386741392 cites W2020658841 @default.
- W4386741392 cites W2026258422 @default.
- W4386741392 cites W2030707267 @default.
- W4386741392 cites W2046120554 @default.
- W4386741392 cites W2052700584 @default.
- W4386741392 cites W2061471485 @default.
- W4386741392 cites W2064711508 @default.
- W4386741392 cites W2065772381 @default.
- W4386741392 cites W2067040999 @default.
- W4386741392 cites W2069047496 @default.
- W4386741392 cites W2075520328 @default.
- W4386741392 cites W2085530204 @default.
- W4386741392 cites W2094299510 @default.
- W4386741392 cites W2100870616 @default.
- W4386741392 cites W2102129515 @default.
- W4386741392 cites W2109289454 @default.
- W4386741392 cites W2109897362 @default.
- W4386741392 cites W2115871947 @default.
- W4386741392 cites W2121196009 @default.
- W4386741392 cites W2121674106 @default.
- W4386741392 cites W2131314720 @default.
- W4386741392 cites W2131374955 @default.
- W4386741392 cites W2136006589 @default.
- W4386741392 cites W2138207763 @default.
- W4386741392 cites W2141208833 @default.
- W4386741392 cites W2142785868 @default.
- W4386741392 cites W2146680808 @default.
- W4386741392 cites W2149790281 @default.
- W4386741392 cites W2149858761 @default.
- W4386741392 cites W2150007935 @default.
- W4386741392 cites W2150474342 @default.
- W4386741392 cites W2150733697 @default.
- W4386741392 cites W2152239989 @default.
- W4386741392 cites W2158019017 @default.
- W4386741392 cites W2159378471 @default.
- W4386741392 cites W2165880713 @default.
- W4386741392 cites W2173885591 @default.
- W4386741392 cites W2179438025 @default.
- W4386741392 cites W2239291357 @default.
- W4386741392 cites W2268729995 @default.
- W4386741392 cites W2270951650 @default.
- W4386741392 cites W2284100402 @default.
- W4386741392 cites W2310533193 @default.
- W4386741392 cites W2342688693 @default.
- W4386741392 cites W2351484480 @default.
- W4386741392 cites W2487764182 @default.
- W4386741392 cites W2517879814 @default.
- W4386741392 cites W2518959324 @default.
- W4386741392 cites W2526262591 @default.
- W4386741392 cites W2527863850 @default.
- W4386741392 cites W2581359536 @default.
- W4386741392 cites W2583285089 @default.
- W4386741392 cites W2612547269 @default.
- W4386741392 cites W2625488274 @default.
- W4386741392 cites W2734775561 @default.
- W4386741392 cites W2740317277 @default.
- W4386741392 cites W2759615793 @default.
- W4386741392 cites W2774787224 @default.
- W4386741392 cites W2777889365 @default.
- W4386741392 cites W2783139678 @default.
- W4386741392 cites W2783378262 @default.
- W4386741392 cites W2794480084 @default.
- W4386741392 cites W2796211669 @default.
- W4386741392 cites W2803895816 @default.
- W4386741392 cites W2804575378 @default.