Attenuated Liver Fibrosis in the Absence of B Cells

Overview

Journal J Clin Invest

Specialty General Medicine

Date 2005 Nov 9

PMID 16276416

Citations 125

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Exploration of a miRNA-mRNA network shared between acute pancreatitis and Epstein-Barr virus infection by integrated bioinformatics analysis.

Wei X, Weng Z, Xu X, Yao J PLoS One. 2024; 19(11):e0311130.

PMID: 39546499 PMC: 11567522. DOI: 10.1371/journal.pone.0311130.

The multifaceted roles of B lymphocytes in metabolic dysfunction-associated steatotic liver disease.

Li H, Xia N Front Immunol. 2024; 15:1447391.

PMID: 39372417 PMC: 11449700. DOI: 10.3389/fimmu.2024.1447391.

Causal association between 731 immunocyte phenotypes and liver cirrhosis: A bidirectional two-sample mendelian randomization analysis.

Li Y, Quan X, Tai Y, Wu Y, Wei B, Wu H World J Hepatol. 2024; 16(8):1156-1166.

PMID: 39221101 PMC: 11362904. DOI: 10.4254/wjh.v16.i8.1156.

The gut microbiota-bile acid axis in cholestatic liver disease.

Sun D, Xie C, Zhao Y, Liao J, Li S, Zhang Y Mol Med. 2024; 30(1):104.

PMID: 39030473 PMC: 11265038. DOI: 10.1186/s10020-024-00830-x.

Role of gut microbiota and immune cells in metabolic-associated fatty liver disease: clinical impact.

Alisi A, McCaughan G, Gronbaek H Hepatol Int. 2024; 18(Suppl 2):861-872.

PMID: 38995341 DOI: 10.1007/s12072-024-10674-6.

References

Golovkina T, Shlomchik M, Hannum L, Chervonsky A . Organogenic role of B lymphocytes in mucosal immunity. Science. 1999; 286(5446):1965-8. DOI: 10.1126/science.286.5446.1965. View

Duffield J, Forbes S, Constandinou C, Clay S, Partolina M, Vuthoori S . Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Invest. 2005; 115(1):56-65. PMC: 539199. DOI: 10.1172/JCI22675. View

Mackay F, Woodcock S, Lawton P, Ambrose C, Baetscher M, Schneider P . Mice transgenic for BAFF develop lymphocytic disorders along with autoimmune manifestations. J Exp Med. 1999; 190(11):1697-710. PMC: 2195729. DOI: 10.1084/jem.190.11.1697. View

Tjandra K, Sharkey K, Swain M . Progressive development of a Th1-type hepatic cytokine profile in rats with experimental cholangitis. Hepatology. 2000; 31(2):280-90. DOI: 10.1002/hep.510310204. View

Baumgarth N, Jager G, Herman O, Herzenberg L . CD4+ T cells derived from B cell-deficient mice inhibit the establishment of peripheral B cell pools. Proc Natl Acad Sci U S A. 2000; 97(9):4766-71. PMC: 18307. DOI: 10.1073/pnas.97.9.4766. View

Crispe I, Dao T, Klugewitz K, Mehal W, Metz D . The liver as a site of T-cell apoptosis: graveyard, or killing field?. Immunol Rev. 2000; 174:47-62. DOI: 10.1034/j.1600-0528.2002.017412.x. View

Vogel S, Piantedosi R, Frank J, Lalazar A, Rockey D, Friedman S . An immortalized rat liver stellate cell line (HSC-T6): a new cell model for the study of retinoid metabolism in vitro. J Lipid Res. 2000; 41(6):882-93. View

Treiner E, Duban L, Bahram S, Radosavljevic M, Wanner V, Tilloy F . Selection of evolutionarily conserved mucosal-associated invariant T cells by MR1. Nature. 2003; 422(6928):164-9. DOI: 10.1038/nature01433. View

Ikeda A, Caldwell R, Longnecker R, Ikeda M . Itchy, a Nedd4 ubiquitin ligase, downregulates latent membrane protein 2A activity in B-cell signaling. J Virol. 2003; 77(9):5529-34. PMC: 153961. DOI: 10.1128/jvi.77.9.5529-5534.2003. View

10.

Nagy L . Recent insights into the role of the innate immune system in the development of alcoholic liver disease. Exp Biol Med (Maywood). 2003; 228(8):882-90. DOI: 10.1177/153537020322800803. View

11.

Whitfield M, Finlay D, Murray J, Troyanskaya O, Chi J, Pergamenschikov A . Systemic and cell type-specific gene expression patterns in scleroderma skin. Proc Natl Acad Sci U S A. 2003; 100(21):12319-24. PMC: 218756. DOI: 10.1073/pnas.1635114100. View

12.

Casola S, Otipoby K, Alimzhanov M, Humme S, Uyttersprot N, Kutok J . B cell receptor signal strength determines B cell fate. Nat Immunol. 2004; 5(3):317-27. DOI: 10.1038/ni1036. View

13.

Wong F, Wen L, Tang M, Ramanathan M, Visintin I, Daugherty J . Investigation of the role of B-cells in type 1 diabetes in the NOD mouse. Diabetes. 2004; 53(10):2581-7. DOI: 10.2337/diabetes.53.10.2581. View

14.

Alt F, Baltimore D . Joining of immunoglobulin heavy chain gene segments: implications from a chromosome with evidence of three D-JH fusions. Proc Natl Acad Sci U S A. 1982; 79(13):4118-22. PMC: 346588. DOI: 10.1073/pnas.79.13.4118. View

15.

Velardi A, Cooper M . An immunofluorescence analysis of the ontogeny of myeloid, T, and B lineage cells in mouse hemopoietic tissues. J Immunol. 1984; 133(2):672-7. View

16.

Desiderio S, Yancopoulos G, Paskind M, Thomas E, Boss M, LANDAU N . Insertion of N regions into heavy-chain genes is correlated with expression of terminal deoxytransferase in B cells. Nature. 1984; 311(5988):752-5. DOI: 10.1038/311752a0. View

17.

Forster I, Rajewsky K . Expansion and functional activity of Ly-1+ B cells upon transfer of peritoneal cells into allotype-congenic, newborn mice. Eur J Immunol. 1987; 17(4):521-8. DOI: 10.1002/eji.1830170414. View

18.

Jungermann K, Katz N . Functional specialization of different hepatocyte populations. Physiol Rev. 1989; 69(3):708-64. DOI: 10.1152/physrev.1989.69.3.708. View

19.

Lafaille J, DeCloux A, Bonneville M, Takagaki Y, Tonegawa S . Junctional sequences of T cell receptor gamma delta genes: implications for gamma delta T cell lineages and for a novel intermediate of V-(D)-J joining. Cell. 1989; 59(5):859-70. DOI: 10.1016/0092-8674(89)90609-0. View

20.

Strohal R, Helmberg A, Kroemer G, Kofler R . Mouse Vk gene classification by nucleic acid sequence similarity. Immunogenetics. 1989; 30(6):475-93. PMC: 7087523. DOI: 10.1007/BF02421180. View