Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Science 4 October 1996:
Vol. 274. no. 5284, pp. 106 - 108
DOI: 10.1126/science.274.5284.106
Prev | Table of Contents | Next

Reports

Requirement for Invariant Chain in B Cell Maturation and Function

Idit Shachar and Richard A. Flavell *

Previously the role of invariant chain (Ii) had been described only as a chaperone that facilitates folding and transport of major histocompatability complex class II molecules; here it is shown that Ii is required for B cell development. B cells from mice lacking Ii were found to have a low response to T-independent type II antigen and could not proliferate after the mice were injected with antigen. Study of cell surface markers revealed a developmental arrest that prevented immature virgin B cells from becoming mature B cells in the periphery. This block was independent of major histocompatability complex class II expression and was an intrinsic feature of B cells that correlated with the amount of Ii. Thus, Ii participates by an unknown mechanism in B cell maturation.

I. Shachar, Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
R. A. Flavell, Section of Immunobiology and Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510, USA.
*   To whom correspondence should be addressed.

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Anti-inflammatory effects of an inflammatory chemokine: CCL2 inhibits lymphocyte homing by modulation of CCL21-triggered integrin-mediated adhesions.
L. Flaishon, G. Hart, E. Zelman, C. Moussion, V. Grabovsky, G. Lapidot Tal, S. Feigelson, R. Margalit, A. Harmelin, T. Avin-Wittenberg, et al. (2008)
Blood 112, 5016-5025
   Abstract »    Full Text »    PDF »
Macrophage Migration Inhibitory Factor Induces B Cell Survival by Activation of a CD74-CD44 Receptor Complex.
Y. Gore, D. Starlets, N. Maharshak, S. Becker-Herman, U. Kaneyuki, L. Leng, R. Bucala, and I. Shachar (2008)
J. Biol. Chem. 283, 2784-2792
   Abstract »    Full Text »    PDF »
IL-15 regulates immature B-cell homing in an Ly49D-, IL-12 , and IL-18 dependent manner.
G. Hart, T. Avin-Wittenberg, and I. Shachar (2008)
Blood 111, 50-59
   Abstract »    Full Text »    PDF »
CD74 induces TAp63 expression leading to B-cell survival.
F. Lantner, D. Starlets, Y. Gore, L. Flaishon, A. Yamit-Hezi, R. Dikstein, L. Leng, R. Bucala, Y. Machluf, M. Oren, et al. (2007)
Blood 110, 4303-4311
   Abstract »    Full Text »    PDF »
IL-8 secreted in a macrophage migration-inhibitory factor- and CD74-dependent manner regulates B cell chronic lymphocytic leukemia survival.
I. Binsky, M. Haran, D. Starlets, Y. Gore, F. Lantner, N. Harpaz, L. Leng, D. M. Goldenberg, L. Shvidel, A. Berrebi, et al. (2007)
PNAS 104, 13408-13413
   Abstract »    Full Text »    PDF »
Genetic Manipulation of CD74 in Mouse Strains of Different Backgrounds Can Result in Opposite Responses to Central Nervous System Injury.
H. Schori, R. Shechter, I. Shachar, and M. Schwartz (2007)
J. Immunol. 178, 163-171
   Abstract »    Full Text »    PDF »
Cell-surface CD74 initiates a signaling cascade leading to cell proliferation and survival.
D. Starlets, Y. Gore, I. Binsky, M. Haran, N. Harpaz, L. Shvidel, S. Becker-Herman, A. Berrebi, and I. Shachar (2006)
Blood 107, 4807-4816
   Abstract »    Full Text »    PDF »
CD74 Is a Member of the Regulated Intramembrane Proteolysis-processed Protein Family.
S. Becker-Herman, G. Arie, H. Medvedovsky, A. Kerem, and I. Shachar (2005)
Mol. Biol. Cell 16, 5061-5069
   Abstract »    Full Text »    PDF »
Tight Regulation of IFN-{gamma} Transcription and Secretion in Immature and Mature B cells by the Inhibitory MHC Class I Receptor, Ly49G2.
G. Hart, L. Flaishon, S. Becker-Herman, and I. Shachar (2005)
J. Immunol. 175, 5034-5042
   Abstract »    Full Text »    PDF »
Restricted MHC-peptide repertoire predisposes to autoimmunity.
N. N. Logunova, C. Viret, L. A. Pobezinsky, S. A. Miller, D. B. Kazansky, J. P. Sundberg, and A. V. Chervonsky (2005)
J. Exp. Med. 202, 73-84
   Abstract »    Full Text »    PDF »
Dissecting MHC Class II Export, B Cell Maturation, and DM Stability Defects in Invariant Chain Mutant Mice.
C. H. Koonce and E. K. Bikoff (2004)
J. Immunol. 173, 3271-3280
   Abstract »    Full Text »    PDF »
Expression of the chemokine receptor CCR2 on immature B cells negatively regulates their cytoskeletal rearrangement and migration.
L. Flaishon, S. Becker-Herman, G. Hart, Y. Levo, W. A. Kuziel, and I. Shachar (2004)
Blood 104, 933-941
   Abstract »    Full Text »    PDF »
Mechanisms Governing B Cell Developmental Defects in Invariant Chain-Deficient Mice.
K. Benlagha, S.-H. Park, R. Guinamard, C. Forestier, L. Karlsson, C.-H. Chang, and A. Bendelac (2004)
J. Immunol. 172, 2076-2083
   Abstract »    Full Text »    PDF »
Ly49D Receptor Expressed on Immature B Cells Regulates Their IFN-{gamma} Secretion, Actin Polymerization, and Homing.
G. Hart, L. Flaishon, S. Becker-Herman, and I. Shachar (2003)
J. Immunol. 171, 4630-4638
   Abstract »    Full Text »    PDF »
MIF Signal Transduction Initiated by Binding to CD74.
L. Leng, C. N. Metz, Y. Fang, J. Xu, S. Donnelly, J. Baugh, T. Delohery, Y. Chen, R. A. Mitchell, and R. Bucala (2003)
J. Exp. Med. 197, 1467-1476
   Abstract »    Full Text »    PDF »
MHC Class II-Associated Invariant Chain Isoforms Regulate Pulmonary Immune Responses.
Q. Ye, P. W. Finn, R. Sweeney, E. K. Bikoff, and R. J. Riese (2003)
J. Immunol. 170, 1473-1480
   Abstract »    Full Text »    PDF »
Severe Immunodeficiency Has Opposite Effects on Neuronal Survival in Glutamate-Susceptible and -Resistant Mice: Adverse Effect of B Cells.
H. Schori, F. Lantner, I. Shachar, and M. Schwartz (2002)
J. Immunol. 169, 2861-2865
   Abstract »    Full Text »    PDF »
Expression and Function of Transgenic HLA-DQ Molecules and Lymphocyte Development in Mice Lacking Invariant Chain.
G. Rajagopalan, M. K. Smart, C. J. Krco, and C. S. David (2002)
J. Immunol. 169, 1774-1783
   Abstract »    Full Text »    PDF »
Id2 Negatively Regulates B Cell Differentiation in the Spleen.
S. Becker-Herman, F. Lantner, and I. Shachar (2002)
J. Immunol. 168, 5507-5513
   Abstract »    Full Text »    PDF »
De Novo Central Nervous System Processing of Myelin Antigen Is Required for the Initiation of Experimental Autoimmune Encephalomyelitis.
S. M. Tompkins, J. Padilla, M. C. Dal Canto, J. P.-Y. Ting, L. Van Kaer, and S. D. Miller (2002)
J. Immunol. 168, 4173-4183
   Abstract »    Full Text »    PDF »
Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity.
D. Matza, F. Lantner, Y. Bogoch, L. Flaishon, R. Hershkoviz, and I. Shachar (2002)
PNAS
   Abstract »    Full Text »    PDF »
Preferential Th1 Immune Response in Invariant Chain-Deficient Mice.
I. Topilski, A. Harmelin, R. A. Flavell, Y. Levo, and I. Shachar (2002)
J. Immunol. 168, 1610-1617
   Abstract »    Full Text »    PDF »
Low Levels of IFN-gamma Down-regulate the Integrin-dependent Adhesion of B Cells by Activating a Pathway That Interferes with Cytoskeleton Rearrangement.
L. Flaishon, F. Lantner, R. Hershkoviz, Y. Levo, and I. Shachar (2001)
J. Biol. Chem. 276, 46701-46706
   Abstract »    Full Text »    PDF »
Autocrine Secretion of Interferon {gamma} Negatively Regulates Homing of Immature B Cells.
L. Flaishon, R. Hershkoviz, F. Lantner, O. Lider, R. Alon, Y. Levo, R. A. Flavell, and I. Shachar (2000)
J. Exp. Med. 192, 1381-1388
   Abstract »    Full Text »    PDF »
Invariant Chain Controls H2-M Proteolysis in Mouse Splenocytes and Dendritic Cells.
P. Pierre, I. Shachar, D. Matza, E. Gatti, R. A. Flavell, and I. Mellman (2000)
J. Exp. Med. 191, 1057-1062
   Abstract »    Full Text »    PDF »
Reduced IL-4-, Lipopolysaccharide-, and IFN-{gamma}-Induced MHC Class II Expression in Mice Lacking Class II Transactivator Due to Targeted Deletion of the GTP-Binding Domain.
Y. Itoh-Lindstrom, J. F. Piskurich, N. J. Felix, Y. Wang, W. J. Brickey, J. L. Platt, B. H. Koller, and J. P.-Y. Ting (1999)
J. Immunol. 163, 2425-2431
   Abstract »    Full Text »    PDF »
Mice lacking all conventional MHC class II genes.
L. Madsen, N. Labrecque, J. Engberg, A. Dierich, A. Svejgaard, C. Benoist, D. Mathis, and L. Fugger (1999)
PNAS 96, 10338-10343
   Abstract »    Full Text »    PDF »
BALB/c Invariant Chain Mutant Mice Display Relatively Efficient Maturation of CD4+ T Cells in the Periphery and Secondary Proliferative Responses Elicited upon Peptide Challenge.
G. Kenty and E. K. Bikoff (1999)
J. Immunol. 163, 232-241
   Abstract »    Full Text »    PDF »
Engagement of B Cell Receptor Regulates the Invariant Chain-Dependent MHC Class II Presentation Pathway.
V. S. Zimmermann, P. Rovere, J. Trucy, K. Serre, P. Machy, F. Forquet, L. Leserman, and J. Davoust (1999)
J. Immunol. 162, 2495-2502
   Abstract »    Full Text »    PDF »
MHC Class II Expression in Double Mutant Mice Lacking Invariant Chain and DM Functions.
G. Kenty, W. D. Martin, L. Van Kaer, and E. K. Bikoff (1998)
J. Immunol. 160, 606-614
   Abstract »    Full Text »    PDF »
Cathepsin S Regulates the Expression of Cathepsin L and the Turnover of gamma -Interferon-inducible Lysosomal Thiol Reductase in B Lymphocytes.
K. Honey, M. Duff, C. Beers, W. H. Brissette, E. A. Elliott, C. Peters, M. Maric, P. Cresswell, and A. Rudensky (2001)
J. Biol. Chem. 276, 22573-22578
   Abstract »    Full Text »    PDF »
Invariant Chain Induces B Cell Maturation by Activating a TAFII105-NF-kappa B-dependent Transcription Program.
D. Matza, O. Wolstein, R. Dikstein, and I. Shachar (2001)
J. Biol. Chem. 276, 27203-27206
   Abstract »    Full Text »    PDF »
Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity.
D. Matza, F. Lantner, Y. Bogoch, L. Flaishon, R. Hershkoviz, and I. Shachar (2002)
PNAS 99, 3018-3023
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)