Attenuated liver fibrosis in the absence of B cells.
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.
Novobrantseva
Tatiana I
TI
Immunology Department, Biogen Idec, Cambridge, Massachusetts 02142, USA. Tatiana.Novobrantseva@biogenidec.com
Majeau
Gerard R
GR
Amatucci
Aldo
A
Kogan
Sophia
S
Brenner
Ian
I
Casola
Stefano
S
Shlomchik
Mark J
MJ
Koteliansky
Victor
V
Hochman
Paula S
PS
Ibraghimov
Alexander
A
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology*; D001483:Base Sequence; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008103:Liver Cirrhosis / Q000378:metabolism / Q000473:pathology*; D008231:Lymphopenia / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology
D003094:Collagen