| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224
IgH and L chain transgenes encoding a phosphocholine (PC)-specific Ig receptor were introduced into recombinase-activating gene (Rag-2-/-) knockout mice. The PC-specific B cells that developed behaved like known autoreactive lymphocytes. They were 1) developmentally arrested in the bone marrow, 2) unable to secrete Ab, 3) able to escape clonal deletion and develop into B1 B cells in the peritoneal cavity, and 4) rescued by overexpression of bcl-2. A second IgL chain was genetically introduced into Rag-2-/- knockout mice expressing the autoreactive PC-specific Ig receptor. These dual L chain-expressing mice had B cells in peripheral lymphoid organs that coexpressed both anti-PC Ab as well as Ab employing the second available L chain that does not generate an autoreactive PC-specific receptor. Coexpression of the additional Ig molecules rescued the autoreactive anti-PC B cells and relieved the functional anergy of the anti-PC-specific B cells, as demonstrated by detection of circulating autoreactive anti-PC-Abs. We call this novel mechanism by which autoreactive B cells can persist by compromising allelic exclusion receptor dilution. Rescue of autoreactive PC-specific B cells would be beneficial to the host because these Abs are vital for protection against pathogens such as Streptococcus pneumoniae.
This article has been cited by other articles:
|
|
 |
|
  Y. Zhang, S. C. Su, D. B. Hecox, G. F. Brady, K. M. Mackin, A. G. Clark, and M. H. Foster Central Tolerance Regulates B Cells Reactive with Goodpasture Antigen {alpha}3(IV)NC1 Collagen J. Immunol., November 1, 2008; 181(9): 6092 - 6100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Shankar, J. C. Nixon, S. Maier, J. Workman, A. D. Farris, and C. F. Webb Anti-Nuclear Antibody Production and Autoimmunity in Transgenic Mice That Overexpress the Transcription Factor Bright J. Immunol., March 1, 2007; 178(5): 2996 - 3006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. M. Fuentes-Panana, G. Bannish, F. G. Karnell, J. F. Treml, and J. G. Monroe Analysis of the Individual Contributions of Ig{alpha} (CD79a)- and Igbeta (CD79b)-Mediated Tonic Signaling for Bone Marrow B Cell Development and Peripheral B Cell Maturation J. Immunol., December 1, 2006; 177(11): 7913 - 7922. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Rui, J. I. Healy, J. Blasioli, and C. C. Goodnow ERK Signaling Is a Molecular Switch Integrating Opposing Inputs from B Cell Receptor and T Cell Cytokines to Control TLR4-Driven Plasma Cell Differentiation J. Immunol., October 15, 2006; 177(8): 5337 - 5346. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Ferry, T. L. Crockford, J. C. H. Leung, and R. J. Cornall Signals from a self-antigen induce positive selection in early B cell ontogeny but are tolerogenic in adults. J. Immunol., June 15, 2006; 176(12): 7402 - 7411. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Sirac, C. Carrion, S. Duchez, I. Comte, and M. Cogne Light chain inclusion permits terminal B cell differentiation and does not necessarily result in autoreactivity PNAS, May 16, 2006; 103(20): 7747 - 7752. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Heltemes-Harris, X. Liu, and T. Manser An antibody VH gene that promotes marginal zone B cell development and heavy chain allelic inclusion Int. Immunol., November 1, 2005; 17(11): 1447 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Liu, M.-G. Velez, J. Humann, S. Rowland, F. J. Conrad, R. Halverson, R. M. Torres, and R. Pelanda Receptor Editing Can Lead to Allelic Inclusion and Development of B Cells That Retain Antibodies Reacting with High Avidity Autoantigens J. Immunol., October 15, 2005; 175(8): 5067 - 5076. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Brummel and P. Lenert Activation of Marginal Zone B Cells from Lupus Mice with Type A(D) CpG-Oligodeoxynucleotides J. Immunol., February 15, 2005; 174(4): 2429 - 2434. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Goodyear, M. Narita, and G. J. Silverman In Vivo VL-Targeted Activation-Induced Apoptotic Supraclonal Deletion by a Microbial B Cell Toxin J. Immunol., March 1, 2004; 172(5): 2870 - 2877. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. F. Widhopf II, D. C. Brinson, T. J. Kipps, and H. Tighe Transgenic Expression of a Human Polyreactive Ig Expressed in Chronic Lymphocytic Leukemia Generates Memory-Type B Cells That Respond to Nonspecific Immune Activation J. Immunol., February 15, 2004; 172(4): 2092 - 2099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Silva, A. L. Kovalchuk, J. S. Kim, G. Klein, and S. Janz BCL2 Accelerates Inflammation-induced BALB/c Plasmacytomas and Promotes Novel Tumors with Coexisting T(12;15) and T(6;15) Translocations Cancer Res., December 15, 2003; 63(24): 8656 - 8663. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Oberdoerffer, T. I. Novobrantseva, and K. Rajewsky Expression of a Targeted {lambda}1 Light Chain Gene Is Developmentally Regulated and Independent of Ig{kappa} Rearrangements J. Exp. Med., May 5, 2003; 197(9): 1165 - 1172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. M. Heltemes and T. Manser Level of B Cell Antigen Receptor Surface Expression Influences Both Positive and Negative Selection of B Cells During Primary Development J. Immunol., August 1, 2002; 169(3): 1283 - 1292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Li, H. Li, and M. Weigert Autoreactive B Cells in the Marginal Zone that Express Dual Receptors J. Exp. Med., January 14, 2002; 195(2): 181 - 188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sanchez, A.-M. Crain-Denoyelle, P. Daras, M.-C. Gendron, and C. Kanellopoulos-Langevin The level of expression of {micro} heavy chain modifies the composition of peripheral B cell subpopulations Int. Immunol., October 1, 2000; 12(10): 1459 - 1466. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
