Attenuated liver fibrosis in the absence of B cells
Tatiana I. Novobrantseva, Gerard R. Majeau, Aldo Amatucci, Sophia Kogan, Ian Brenner, Stefano Casola, Mark J. Shlomchik, Victor Koteliansky, Paula S. Hochman, Alexander Ibraghimov
Tatiana I. Novobrantseva, Gerard R. Majeau, Aldo Amatucci, Sophia Kogan, Ian Brenner, Stefano Casola, Mark J. Shlomchik, Victor Koteliansky, Paula S. Hochman, Alexander Ibraghimov
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Research Article Immunology

Attenuated liver fibrosis in the absence of B cells

Abstract

Analysis of mononuclear cells in the adult mouse liver revealed that B cells represent as much as half of the intrahepatic lymphocyte population. Intrahepatic B cells (IHB cells) are phenotypically similar to splenic B2 cells but express lower levels of CD23 and CD21 and higher levels of CD5. IHB cells proliferate as well as splenic B cells in response to anti-IgM and LPS stimulation in vitro. VDJ gene rearrangements in IHB cells contain insertions of N,P region nucleotides characteristic of B cells maturing in the adult bone marrow rather than in the fetal liver. To evaluate whether B cells can have an impact on liver pathology, we compared CCl4-induced fibrosis development in B cell–deficient and wild-type mice. CCl4 caused similar acute liver injury in mutant and wild-type mice. However, following 6 weeks of CCl4 treatment, histochemical analyses showed markedly reduced collagen deposition in B cell–deficient as compared with wild-type mice. By analyzing mice that have normal numbers of B cells but lack either T cells or immunoglobulin in the serum, we established that B cells have an impact on fibrosis in an antibody- and T cell–independent manner.

Authors

Tatiana I. Novobrantseva, Gerard R. Majeau, Aldo Amatucci, Sophia Kogan, Ian Brenner, Stefano Casola, Mark J. Shlomchik, Victor Koteliansky, Paula S. Hochman, Alexander Ibraghimov

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B cells mediate antibody-independent effects on CCl4-induced liver fibro...
B cells mediate antibody-independent effects on CCl4-induced liver fibrosis. (A) Mice expressing Epstein-Barr virus–derived protein LMP2a from a gene incorporated at the place of J elements of the IgH locus that lack both surface and circulating immunoglobulin, (B) mIgM-Tg (JH–/–) mice expressing surface but not secreted Ig, and corresponding WT control mice were gavaged with 1.75 ml/kg of CCl4 or with mineral oil. One week after the sixth weekly treatment, mice were sacrificed, collagen-specific Sirius red staining of liver sections was performed, and interstitial collagen deposition was quantified. A column of dots represents a series of sections from 1 animal; mean values are shown as red bars.