The immunoglobulin heavy-chain locus hs3b and hs4 3' enhancers are dispensable for VDJ assembly and somatic hypermutation.
type: Dataset
description: The more distal enhancers of the immunoglobulin heavy-chain 3' regulatory region, hs3b and hs4, were recently demonstrated as master control elements of germline transcription and class switch recombination to most immunoglobulin constant genes. In addition, they were shown to enhance the accumulation of somatic mutations on linked transgenes. Since somatic hypermutation and class switch recombination are tightly linked processes, their common dependency on the endogenous locus 3' enhancers could be an attractive hypothesis. VDJ structure and somatic hypermutation were analyzed in B cells from mice carrying either a heterozygous or a homozygous deletion of these enhancers. We find that hs3b and hs4 are dispensable both for VDJ assembly and for the occurrence of mutations at a physiologic frequency in the endogenous locus. In addition, we show that cells functionally expressing the immunoglobulin M (IgM) class B-cell receptor encoded by an hs3b/hs4-deficient locus were fully able to enter germinal centers, undergo affinity maturation, and yield specific antibody responses in homozygous mutant mice, where IgG1 antibodies compensated for the defect in other IgG isotypes. By contrast, analysis of Peyer patches from heterozygous animals showed that peanut agglutinin (PNAhigh) B cells functionally expressing the hs3b/hs4-deficient allele were dramatically outclassed by B cells expressing the wild-type locus and normally switching to IgA. This study thus also highlights the role of germinal centers in the competition between B cells for affinity maturation and suggests that membrane IgA may promote recruitment in an activated B-cell compartment, or proliferation of activated B cells, more efficiently than IgM in Peyer patches.
issued: 2026-05-26T01:45:44.228434
language: en
modified: 2026-05-26T01:45:44.228441
contact point: Organization
  fn: CCSD
keyword: infoeu-reposemanticsarticle
keyword: journal-articles
keyword: mesh-alleles
keyword: mesh-animals
keyword: mesh-b-lymphocytes
keyword: mesh-base-sequence
keyword: mesh-cloning-molecular
keyword: mesh-enhancer-elements-genetics
keyword: mesh-gene-rearrangement-b-lymphocyte-heavy-chain
keyword: mesh-immunoglobulin-heavy-chains
keyword: mesh-immunoglobulin-joining-region
keyword: mesh-immunoglobulin-variable-region
keyword: mesh-immunoglobulins
keyword: mesh-introns
keyword: mesh-locus-control-region
keyword: mesh-mice
keyword: mesh-mice-inbred-c57bl
keyword: mesh-mice-knockout
keyword: mesh-molecular-sequence-data
keyword: mesh-mutation
keyword: mesh-peyers-patches
keyword: mesh-sequence-deletion
keyword: nlm
keyword: sdvimmlife-sciences-q-bioimmunology
landing page: 0006-4971

The immunoglobulin heavy-chain locus hs3b and hs4 3' enhancers are dispensable for VDJ assembly and somatic hypermutation.
type: Distribution
format: HTML
issued: 2026-05-26T01:45:44.407867
modified: 2026-05-26T01:45:44.168560
access URL: https://hal.science/hal-00023823

test_moissonnage_selune
type: Agent