Dual immunoglobulin light chain B cells: Trojan horses of autoimmunity?

被引:29
作者
Pelanda, Roberta [1 ,2 ]
机构
[1] Natl Jewish Hlth, Integrated Dept Immunol, Denver, CO 80206 USA
[2] Univ Colorado, Sch Med, Denver, CO 80206 USA
关键词
POSITIVE SELECTION; ALLELIC INCLUSION; NEGATIVE SELECTION; ESCAPE TOLERANCE; ANTIGEN RECEPTOR; SELF-ANTIGEN; BONE-MARROW; MICE; LYMPHOCYTES; REPERTOIRE;
D O I
10.1016/j.coi.2014.01.012
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Receptor editing, a major mechanism of B cell tolerance, can also lead to allelic inclusion at the immunoglobulin light chain loci and the development of B cells that coexpress two different immunoglobulin light chains and, therefore, two antibody specificities. Most allelically included B cells express two K chains, although rare dual-k cells are also observed. Moreover, these cells typically coexpress an autoreactive and a nonautoreactive antibody. Thus, allelically included B cells could operate like 'Trojan horses': expression and function of the nonautoreactive antigen receptors might promote their maturation, activation, and terminal differentiation into effector cells that also express and secrete autoantibodies. Indeed, dual-K B cells are greatly expanded into effector B cell subsets in some autoimmune mice, thus indicating they might play an important role in disease.
引用
收藏
页码:53 / 59
页数:7
相关论文
共 42 条
[1]   An immunoglobulin Cκ-reactive single chain antibody fusion protein induces tolerance through receptor editing in a normal polyclonal immune system [J].
Ait-Azzouzene, D ;
Verkoczy, L ;
Peters, J ;
Gavin, A ;
Skog, P ;
Vela, JL ;
Nemazee, D .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (05) :817-828
[2]   Global analysis of B cell selection using an immunoglobulin light chain-mediated model of autoreactivity [J].
Andrews, Sarah F. ;
Zhang, Qingzhao ;
Lim, Samuel ;
Li, Lie ;
Lee, Jane-Hwei ;
Zheng, Nai-Ying ;
Huang, Min ;
Taylor, William M. ;
Farris, A. Darise ;
Ni, Dongyao ;
Meng, Wenzhao ;
Prak, Eline T. Luning ;
Wilson, Patrick C. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2013, 210 (01) :125-142
[3]   Ligand-independent signaling functions for the B lymphocyte antigen receptor and their role in positive selection during B lymphopoiesis [J].
Bannish, G ;
Fuentes-Pananá, EM ;
Cambier, JC ;
Pear, WS ;
Monroe, JG .
JOURNAL OF EXPERIMENTAL MEDICINE, 2001, 194 (11) :1583-1596
[4]   Negative Selection by IgM Superantigen Defines a B Cell Central Tolerance Compartment and Reveals Mutations Allowing Escape [J].
Bao Hoa Duong ;
Ota, Takayuki ;
Aoki-Ota, Miyo ;
Cooper, Anthony Byron ;
Ait-Azzouzene, Djemel ;
Vela, Jose Luis ;
Gavin, Amanda Lee ;
Nemazee, David .
JOURNAL OF IMMUNOLOGY, 2011, 187 (11) :5596-5605
[5]   Frequency and characterization of phenotypic Ig heavy chain allelically included IgM-expressing B cells in mice [J].
Barreto, V ;
Cumano, A .
JOURNAL OF IMMUNOLOGY, 2000, 164 (02) :893-899
[6]   A hypomorphic IgH-chain allele affects development of B-cell subsets and favours receptor editing [J].
Brenner, Sven ;
Drewel, Diana ;
Steinbart, Thomas ;
Weisel, Florian ;
Haertel, Eric ;
Poetzsch, Sonja ;
Welzel, Heike ;
Brandl, Andreas ;
Yu, Philipp ;
Mudde, Geert C. ;
Schweizer, Astrid ;
Nitschke, Lars ;
Winkler, Thomas H. .
EMBO JOURNAL, 2011, 30 (13) :2705-2718
[7]   Contribution of receptor editing to the antibody repertoire [J].
Casellas, R ;
Shih, TAY ;
Kleinewietfeld, M ;
Rakonjac, J ;
Nemazee, D ;
Rajewsky, K ;
Nussenzweig, MC .
SCIENCE, 2001, 291 (5508) :1541-1544
[8]   Igκ allelic inclusion is a consequence of receptor editing [J].
Casellas, Rafael ;
Zhang, Qingzhao ;
Zheng, Nai-Ying ;
Mathias, Melissa D. ;
Smith, Kenneth ;
Wilson, Patrick C. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2007, 204 (01) :153-160
[9]   Antigen-induced exclusion from follicles and anergy are separate and complementary processes that influence peripheral B cell fate [J].
Cyster, JG ;
Goodnow, CC .
IMMUNITY, 1995, 3 (06) :691-701
[10]   Dual-reactive B cells are autoreactive and highly enriched in the plasmablast and memory B cell subsets of autoimmune mice [J].
Fournier, Emilie M. ;
Velez, Maria-Gabriela ;
Leahy, Katelyn ;
Swanson, Cristina L. ;
Rubtsov, Anatoly V. ;
Torres, Raul M. ;
Pelanda, Roberta .
JOURNAL OF EXPERIMENTAL MEDICINE, 2012, 209 (10) :1797-1812