Dissecting MHC Class II Export, B Cell Maturation, and DM Stability Defects in Invariant Chain Mutant Mice

Pro-B cells are early B-cell progenitors that retain macrophage potential. We have studied MHC class II molecules and invariant chain inducibility on four class II negative mouse pro- B-cell clones. We analyzed the effects of IL-4 and IFN-γ, which represent the major inducers of class II in the B-lymphoid and monocytic/macrophage lineages, respectively. After 48 h of treatment with either cytokine, three pro-B-cell clones (C2.13, A1.5, and F2.2) expressed intracellular invariant chain and cell-surface class II molecules. One clone (D2.1) remained negative. As already reported, more differentiated 70Z/3 pre-B cells were inducible by IL-4 only. These data suggest that the induction of class II and invariant-chain genes are subject to regulation throughout B-cell differentiation.

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Invariant Chain Induces B Cell Maturation by Activating a TAFII105-NF-κB-dependent Transcription Program

Journal of Biological Chemistry ◽

10.1074/jbc.m104684200 ◽

2001 ◽

Vol 276 (29) ◽

pp. 27203-27206 ◽

Cited By ~ 75

Author(s):

Didi Matza ◽

Orit Wolstein ◽

Rivka Dikstein ◽

Idit Shachar

Keyword(s):

B Cell ◽

Cell Maturation ◽

Invariant Chain ◽

B Cell Maturation ◽

Transcription Program

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Invariant chain induces B cell maturation in a process that is independent of its chaperonic activity

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.052703299 ◽

2002 ◽

Vol 99 (5) ◽

pp. 3018-3023 ◽

Cited By ~ 55

Author(s):

D. Matza ◽

F. Lantner ◽

Y. Bogoch ◽

L. Flaishon ◽

R. Hershkoviz ◽

...

Keyword(s):

B Cell ◽

Cell Maturation ◽

Invariant Chain ◽

B Cell Maturation

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Requirement for Invariant Chain in B Cell Maturation and Function

Science ◽

10.1126/science.274.5284.106 ◽

1996 ◽

Vol 274 (5284) ◽

pp. 106-108 ◽

Cited By ~ 86

Author(s):

I. Shachar ◽

R. A. Flavell

Keyword(s):

B Cell ◽

Cell Maturation ◽

Invariant Chain ◽

B Cell Maturation ◽

And Function

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Internalization and catabolism of radiolabelled antibodies to the MHC class-II invariant chain by B-cell lymphomas

Biochemical Journal ◽

10.1042/bj3200293 ◽

1996 ◽

Vol 320 (1) ◽

pp. 293-300 ◽

Cited By ~ 60

Author(s):

Hans J HANSEN ◽

Gaik Lin ONG ◽

Habibe DIRIL ◽

Anita VALDEZ ◽

Paul A. ROCHE ◽

...

Keyword(s):

B Cell ◽

Mhc Class Ii ◽

Class Ii ◽

Invariant Chain ◽

B Cell Lymphomas ◽

Cell Content ◽

Radiolabelled Antibodies ◽

Uptake Process ◽

Reliable Marker ◽

Class Ii Antigen

The fate of antibody (Ab) LL1, which reacts with the invariant chain (Ii) subunit of the immature MHC class-II antigen (CD74) after binding to the surface of B-cell lymphomas was investigated. This Ab was internalized and catabolized very rapidly, much faster than other Abs that are considered to be rapidly internalized, such as CD19, CD22 and anti-(transferrin receptor). Such internalization did not depend on Ab cross-linking. The capacity of this uptake process was determined in long-term experiments by increasing the Ab concentration: in 1 day, approx. 8×106 Ab molecules per cell were catabolized. This analysis was facilitated by the use of radiolabels that are trapped within cells after catabolism of the Abs to which they were conjugated. If the Ab is a reliable marker for the Ii antigen, which is likely, we can conclude that Ii directed to the cell surface appears to be sufficient, indeed more than sufficient, to account for the cell content of mature class-II molecules.

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The Influence of MHC Class II on B Cell Defects Induced by Invariant Chain/CD74 N-Terminal Fragments

The Journal of Immunology ◽

10.4049/jimmunol.1601533 ◽

2017 ◽

Vol 199 (1) ◽

pp. 172-185 ◽

Cited By ~ 7

Author(s):

Janna Schneppenheim ◽

Ann-Christine Loock ◽

Susann Hüttl ◽

Michaela Schweizer ◽

Renate Lüllmann-Rauch ◽

...

Keyword(s):

B Cell ◽

Mhc Class Ii ◽

Class Ii ◽

Invariant Chain

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Dynamics of Major Histocompatibility Complex Class II Compartments during B Cell Receptor–mediated Cell Activation

Journal of Experimental Medicine ◽

10.1084/jem.20011543 ◽

2002 ◽

Vol 195 (4) ◽

pp. 461-472 ◽

Cited By ~ 82

Author(s):

Danielle Lankar ◽

Hélène Vincent-Schneider ◽

Volker Briken ◽

Takeaki Yokozeki ◽

Graça Raposo ◽

...

Keyword(s):

B Cells ◽

B Cell ◽

Mhc Class Ii ◽

Cell Receptor ◽

Class Ii ◽

B Cell Receptor ◽

Cathepsin S ◽

Invariant Chain ◽

Histocompatibility Complex ◽

Mhc Class Ii Molecules

Antigen recognition by clonotypic B cell receptor (BcR) is the first step of B lymphocytes differentiation into plasmocytes. This B cell function is dependent on efficient major histocompatibility complex (MHC) class II–restricted presentation of BcR-bound antigens. In this work, we analyzed the subcellular mechanisms underlying antigen presentation after BcR engagement on B cells. In quiescent B cells, we found that MHC class II molecules mostly accumulated at the cell surface and in an intracellular pool of tubulovesicular structures, whereas H2-M molecules were mostly detected in distinct lysosomal compartments devoid of MHC class II. BcR stimulation induced the transient intracellular accumulation of MHC class II molecules in newly formed multivesicular bodies (MVBs), to which H2-M was recruited. The reversible downregulation of cathepsin S activity led to the transient accumulation of invariant chain–MHC class II complexes in MVBs. A few hours after BcR engagement, cathepsin S activity increased, the p10 invariant chain disappeared, and MHC class II–peptide complexes arrived at the plasma membrane. Thus, BcR engagement induced the transient formation of antigen-processing compartments, enabling antigen-specific B cells to become effective antigen-presenting cells.

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