B cells from rheumatoid arthritis patients show important alterations in the expression of CD86 and FcgammaRIIb, which are modulated by anti-tumor necrosis factor therapy.
BACKGROUND
Several molecules help preserve peripheral B cell tolerance, but when altered, they may predispose to autoimmunity. This work studied the expression of the costimulatory molecule CD86 and the inhibitory receptor for IgG immune complexes FcgammaRIIb (CD32b), on B cells from rheumatoid arthritis (RA) patients, and the influence of anti-tumor necrosis factor (TNF) therapy.


METHODS
Peripheral B cells from 18 RA patients and 13 healthy donors were characterized using flow cytometry. Eleven patients who underwent a six-month adalimumab therapy were further assessed for phenotypic changes on their B cells.


RESULTS
RA patients exhibited a high percentage of naïve and memory B cells expressing CD86. In contrast, expression of FcgammaRIIb was significantly reduced on RA memory B cells and plasmablasts as compared to healthy donors, probably due to downregulation of this receptor when differentiating from naïve to memory cells. These alterations on FcgammaRIIb were associated with high levels of anti-citrullinated vimentin autoantibodies. In addition, treatment with adalimumab normalized the expression of CD86 on memory B cells and reduced the expression of FcgammaRIIb, mainly on naïve B cells.


CONCLUSIONS
Our findings show that peripheral B cells from RA patients have an altered expression of key molecules, such as CD86 and FcgammaRIIb. Because this latter receptor is required for feedback inhibition, a deficient expression might contribute to humoral autoimmune responses. Furthermore, these molecules are likely to be influenced by inflammatory factors, since they were modulated by TNF inhibition.
Catalán
Diego
D
Programa Disciplinario de Inmunología, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Avenida Independencia 1027, Santiago, Chile.
Aravena
Octavio
O
Sabugo
Francisca
F
Wurmann
Pamela
P
Soto
Lilian
L
Kalergis
Alexis M
AM
Cuchacovich
Miguel
M
Aguillón
Juan C
JC
D000068879:Adalimumab; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D051940:B7-2 Antigen / Q000378:metabolism*; D005260:Female; D006801:Humans; D007596:Joints / Q000503:physiopathology; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D017452:Receptors, IgG / Q000378:metabolism*; D012720:Severity of Illness Index; D014746:Vimentin / Q000276:immunology
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001323:Autoantibodies; D051940:B7-2 Antigen; C497964:CD86 protein, human; C499173:FCGR2B protein, human; D010456:Peptides, Cyclic; D017452:Receptors, IgG; D014746:Vimentin; C487763:cyclic citrullinated peptide; D000068879:Adalimumab
Science. 2005 Jan 28;307(5709):590-3
15681388
Clin Exp Immunol. 1999 Mar;115(3):554-60
10193433
J Leukoc Biol. 2005 May;77(5):767-76
15703199
Arthritis Res Ther. 2007;9(3):R51
17521421
Arthritis Rheum. 2008 Feb;58(2):384-8
18240208
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):2910-5
15703291
J Exp Med. 2008 Apr 14;205(4):883-95
18362174
Ann Rheum Dis. 2001 May;60(5):523-6
11302879
J Allergy Clin Immunol. 1998 Jan;101(1 Pt 1):96-102
9449507
J Immunol. 2008 Jan 15;180(2):1276-84
18178868
Clin Immunol Immunopathol. 1997 Jun;83(3):199-204
9175908
Arthritis Rheum. 2004 Jun;50(6):1918-27
15188368
Eur J Immunol. 2008 Aug;38(8):2241-50
18604868
J Immunol. 2007 Mar 1;178(5):3272-80
17312177
Hum Mol Genet. 2005 Oct 1;14(19):2881-92
16115811
J Exp Med. 2000 May 1;191(9):1611-6
10790435
J Immunol. 2009 Jan 15;182(2):890-901
19124732
J Leukoc Biol. 2006 Jan;79(1):59-70
16244114
Ann N Y Acad Sci. 2003 Apr;987:246-8
12727646
Arthritis Rheum. 2004 Dec;50(12):3878-87
15593228
Nat Rev Immunol. 2008 Jan;8(1):34-47
18064051
Immunity. 1999 Apr;10(4):451-61
10229188
Arthritis Rheum. 2002 May;46(5):1242-54
12115230
J Immunol. 2007 Oct 15;179(8):5109-16
17911596
J Immunol. 2005 Mar 15;174(6):3781-8
15749919
Cell Immunol. 2002 Mar-Apr;216(1-2):50-64
12381350
Nat Med. 2005 Oct;11(10):1056-8
16170323
Hum Genet. 2005 Jul;117(2-3):220-7
15895258
Immunogenetics. 2000 May;51(6):429-35
10866109
Arthritis Rheum. 1988 Mar;31(3):315-24
3358796
Arthritis Res Ther. 2008;10(6):R142
19077182
Rheumatology (Oxford). 2005 Jun;44(6):729-34
15757966
Immunity. 2000 Aug;13(2):277-85
10981970
BMC Immunol. 2008 Jul 24;9:39
18652679
N Engl J Med. 2004 Jun 17;350(25):2572-81
15201414
Clin Exp Rheumatol. 2008 Jan-Feb;26(1):89-95
18328152
Genes Immun. 2008 Dec;9(8):680-8
18633424
Arthritis Rheum. 1998 Oct;41(10):1845-50
9778226
J Immunol. 2001 Oct 15;167(8):4710-8
11591802
Scand J Immunol. 2007 Nov;66(5):584-90
17868260
Arthritis Res Ther. 2006;8(4):R119
16859519
J Exp Med. 1999 Jan 4;189(1):187-94
9874575
J Immunol. 2006 Dec 15;177(12):8440-7
17142741
Proc Natl Acad Sci U S A. 2009 Mar 24;106(12):4788-92
19261857
Clin Immunol. 2005 Oct;117(1):78-86
16084773
J Immunol. 2000 Nov 15;165(10):5970-9
11067960
J Exp Med. 2006 Sep 4;203(9):2157-64
16923849
J Exp Med. 2002 Jun 17;195(12):1653-9
12070293
Arthritis Rheum. 1995 Jan;38(1):44-8
7818570
Int Immunol. 2008 Feb;20(2):185-92
18182380
Neurogastroenterol Motil. 2009 Jun;21(6):644-50, e27
19222763
J Immunol. 2001 Jan 1;166(1):531-7
11123333
Arthritis Rheum. 2006 Dec;54(12):3828-37
17133580