| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Microbiology and Immunology and
Anatomy and Neurobiology, Immunology Group, Virginia Commonwealth University, Richmond, VA 23298
It is believed that Ag in immune complexes (ICs) on follicular dendritic cells (FDCs) selects high affinity B cells and promotes affinity maturation. However, selection has been documented in the absence of readily detectable ICs on FDCs, suggesting that FDC-ICs may not be important. These results prompted experiments to test the hypothesis that IC-bearing murine FDCs can promote high affinity IgG responses by selecting B cells after stimulating naive IgM+ cells to mature and class switch. Coculturing naive 
+ B cells, FDCs, (4-hydroxy-3-nitrophenyl)acetyl-chicken 
-globulin (CGG) + anti-CGG ICs, and CGG-primed T cells resulted in FDC-lymphocyte clusters and production of anti-4-hydroxy-5-iodo-3-nitrophenyl acetyl. Class switching was indicated by a shift from IgM to IgG, and affinity maturation was indicated by a change from mostly low affinity IgM and IgG in the first week to virtually all high affinity IgG anti-4-hydroxy-5-iodo-3-nitrophenyl acetyl in the second week. Class switching and affinity maturation were easily detectable in the presence of FDCs bearing appropriate ICs, but not in the absence of FDCs. Free Ag plus FDCs resulted in low affinity IgG, but affinity maturation was only apparent when FDCs bore ICs. Class switching is activation-induced cytidine deaminase (AID) dependent, and blocking FDC-CD21 ligand-B cell CD21 interactions inhibited FDC-IC-mediated enhancement of AID production and the IgG response. In short, these data support the concept that ICs on FDCs can promote AID production, class switching, and maturation of naive IgM+ B cells, and further suggest that the IC-bearing FDCs help select high affinity B cells that produce high affinity IgG.
This article has been cited by other articles:
|
|
 |
|
  N. Tonomura, K. Habiro, A. Shimizu, M. Sykes, and Y.-G. Yang Antigen-specific human T-cell responses and T cell-dependent production of human antibodies in a humanized mouse model Blood, April 15, 2008; 111(8): 4293 - 4296. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Wu, S. Sukumar, M. E. El Shikh, A. M. Best, A. K. Szakal, and J. G. Tew Immune Complex-Bearing Follicular Dendritic Cells Deliver a Late Antigenic Signal That Promotes Somatic Hypermutation J. Immunol., January 1, 2008; 180(1): 281 - 290. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. M. El Shikh, R. M. El Sayed, Y. Wu, A. K. Szakal, and J. G. Tew TLR4 on Follicular Dendritic Cells: An Activation Pathway That Promotes Accessory Activity J. Immunol., October 1, 2007; 179(7): 4444 - 4450. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. E. NYDEGGER Immune Complex Pathophysiology Ann. N.Y. Acad. Sci., August 1, 2007; 1109(1): 66 - 83. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Nishikawa, M. Hikida, M. Magari, N. Kanayama, M. Mori, H. Kitamura, T. Kurosaki, and H. Ohmori Establishment of Lymphotoxin beta Receptor Signaling-Dependent Cell Lines with Follicular Dendritic Cell Phenotypes from Mouse Lymph Nodes J. Immunol., October 15, 2006; 177(8): 5204 - 5214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Sukumar, D. H. Conrad, A. K. Szakal, and J. G. Tew Differential T Cell-Mediated Regulation of CD23 (Fc{epsilon}RII) in B Cells and Follicular Dendritic Cells. J. Immunol., April 15, 2006; 176(8): 4811 - 4817. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
