Attenuated liver fibrosis in the absence of B cells
Tatiana I. Novobrantseva, … , Paula S. Hochman, Alexander Ibraghimov
Tatiana I. Novobrantseva, … , Paula S. Hochman, Alexander Ibraghimov
Published November 1, 2005
Citation Information: J Clin Invest. 2005;115(11):3072-3082. https://doi.org/10.1172/JCI24798.
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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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Figure 2

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The degree of liver fibrogenesis is proportionate to B cell numbers. Mic...
The degree of liver fibrogenesis is proportionate to B cell numbers. Mice were gavaged with 3.5 ml/kg (A and B and C, left panel) or 1.75 ml/kg (C, right panel, and D) of CCl4 or mineral oil. Each plot represents 1 experiment. (A) JH–/– and BALB/c WT control mice were bled 24 hours after a single CCl4 or oil administration, and ALT levels were measured. A representative experiment out of 3 is shown. (B–D) One week after the sixth weekly treatment of oil or CCl4, mice were sacrificed, and collagen-specific Sirius red staining of liver sections was performed to quantify interstitial collagen deposition in JH–/– and WT BALB/c mice (C) or in WT C57BL/6 and BAFF-Tg mice (D). Magnification, ×50. In each case, a representative experiment out of at least 2 is shown. A column of dots represents a series of sections from 1 animal; mean values are depicted as red bars.