Abstract
The IgH 3' regulatory region (3'RR), encompassing the four transcriptional enhancers hs3a-hs1,2-hs3b-hs4, is a potent lymphoma oncogene deregulator but its role in B cell-mediated inflammatory responses is unknown. We investigated the 3'RR involvement in the in vivo pristane-induced inflammatory response in BALB/c mice. The lack of the 3'RR in BALB/c mice had no wide effect on the incidence, the kinetic of development and the cellular composition of peritoneal ascites. Ascite pro-inflammatory cytokines levels (IL-6, IL-21, IL-12/23, TNF-α) were unchanged while anti-inflammatory cytokines levels (IL-10, interferon-γ) were slightly increased in 3'RR-deficient BALB/c mice as compared to wt BALB/c mice. In conclusion, the 3'RR is dispensable for the efficient recruitment of immune cells and the normal development of an inflammatory response in the in vivo pristane-induced inflammatory model. The 3'RR might be considered as a potential suitable target for anti-lymphoma pharmacological therapy without potent adverse effect on normal immune and inflammatory responses.
Highlights
The IgH locus undergoes multiple changes along B cell differentiation, affecting transcription and accessibility to V(D)J recombination, somatic hypermutation (SHM) and class switch recombination (CSR) [1, 2]
Some phenotypes due to specific mutation are independent of the genetic background, phenotypic variability often becomes apparent only when a given mutation is studied on various genetic backgrounds [1821]
Some phenotypes due to specific mutations are independent of the genetic background, phenotypic variability often becomes apparent only when a given mutation is studied on various genetic backgrounds
Summary
The IgH locus undergoes multiple changes along B cell differentiation, affecting transcription and accessibility to V(D)J recombination, somatic hypermutation (SHM) and class switch recombination (CSR) [1, 2]. The 3’RR is, considered as a potential lymphoma oncogene deregulator Strengthening this issue, transgenic mice models demonstrate the 3’RR implication in the development of several B cell lymphomas such as Burkitt lymphomas, mantle cell lymphomas and anaplastic B cell lymphomas [8,9,10,11,12,13,14,15] leading to the conclusion that the 3’RR might be a potential target for anti-lymphoma pharmacological therapy. Such approach would be promising if targeting the 3’RR does not induce adverse effects such as altered normal immune and inflammatory responses. The i.p. pristane injection induces the development of a chronic inflammatory response with an influx of T cells, B cells and granulocytic cells into the peritoneal cavity as well as the development of ascites; functional B cells being critical for all these events [16, 17]
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