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

2002 ◽  
Vol 195 (4) ◽  
pp. 461-472 ◽  
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.

scholarly journals Both IFN-γ and IL-4 Induce MHC Class II Expression at the Surface of Mouse Pro-B Cells

1997 ◽  
Vol 5 (2) ◽  
pp. 115-120 ◽  
Author(s):  
Suzanne Lombard-Platet ◽  
Valerie Meyer ◽  
Rhodri Ceredig
Keyword(s):  
B Cells ◽  
B Cell ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Invariant Chain ◽  
B Cell Differentiation ◽  
Cell Clones ◽  
Ifn Γ ◽  
B Lymphoid ◽  
Mhc Class Ii Molecules

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.

scholarly journals Major Histocompatibility Complex Class II Compartments in Human and Mouse B Lymphoblasts Represent Conventional Endocytic Compartments

1997 ◽  
Vol 139 (3) ◽  
pp. 639-649 ◽  
Author(s):  
Monique J. Kleijmeer ◽  
Stanislaw Morkowski ◽  
Janice M. Griffith ◽  
Alexander Y. Rudensky ◽  
Hans J. Geuze
Keyword(s):  
Major Histocompatibility Complex ◽  
B Cells ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Invariant Chain ◽  
Histocompatibility Complex ◽  
Peptide Complexes ◽  
Endocytic Compartments ◽  
Human And Mouse ◽  
Mhc Class Ii Molecules

In most human and mouse antigen-presenting cells, the majority of intracellular major histocompatibility complex (MHC) class II molecules resides in late endocytic MHC class II compartments (MIICs), thought to function in antigen processing and peptide loading. However, in mouse A20 B cells, early endocytic class II-containing vesicles (CIIVs) have been reported to contain most of the intracellular MHC class II molecules and have also been implicated in formation of MHC class II–peptide complexes. To address this discrepancy, we have studied in great detail the endocytic pathways of both a human (6H5.DM) and a mouse (A20.Ab) B cell line. Using quantitative immunoelectron microscopy on cryosections of cells that had been pulse–chased with transferrin-HRP or BSA-gold as endocytic tracers, we have identified up to six endocytic subcompartments including an early MIIC type enriched in invariant chain, suggesting that it serves as an important entrance to the endocytic pathway for newly synthesized MHC class II/invariant chain complexes. In addition, early MIICs represented the earliest endocytic compartment containing MHC class II– peptide complexes, as shown by using an antibody against an abundant endogenous class II–peptide complex. The early MIIC exhibited several though not all of the characteristics reported for the CIIV and was situated just downstream of early endosomes. We have not encountered any special class II-containing endocytic structures besides those normally present in nonantigen-presenting cells. Our results therefore suggest that B cells use conventional endocytic compartments rather than having developed a unique compartment to accomplish MHC class II presentation.

scholarly journals Delivery of B Cell Receptor–internalized Antigen to Endosomes and Class II Vesicles

1997 ◽  
Vol 186 (8) ◽  
pp. 1299-1306 ◽  
Author(s):  
James R. Drake ◽  
Paul Webster ◽  
John C. Cambier ◽  
Ira Mellman
Keyword(s):  
B Cells ◽  
B Cell ◽  
Antigen Processing ◽  
Specific Antigen ◽  
Cell Receptor ◽  
Class Ii ◽  
Time Frame ◽  
B Cell Receptor ◽  
Subcellular Compartment ◽  
Endocytic Vesicles

B cell receptor (BCR)-mediated antigen processing is a mechanism that allows class II–restricted presentation of specific antigen by B cells at relatively low antigen concentrations. Although BCR-mediated antigen processing and class II peptide loading may occur within one or more endocytic compartments, the functions of these compartments and their relationships to endosomes and lysosomes remain uncertain. In murine B cells, at least one population of class II– containing endocytic vesicles (i.e., CIIV) has been identified and demonstrated to be distinct both physically and functionally from endosomes and lysosomes. We now demonstrate the delivery of BCR-internalized antigen to CIIV within the time frame during which BCR-mediated antigen processing and formation of peptide–class II complexes occurs. Only a fraction of the BCR-internalized antigen was delivered to CIIV, with the majority of internalized antigen being delivered to lysosomes that are largely class II negative. The extensive colocalization of BCR-internalized antigen and newly synthesized class II molecules in CIIV suggests that CIIV may represent a specialized subcellular compartment for BCR-mediated antigen processing. Additionally, we have identified a putative CIIV-marker protein, immunologically related to the Igα subunit of the BCR, which further illustrates the unique nature of these endocytic vesicles.

scholarly journals Negligible Class II MHC Presentation of B Cell Receptor-Derived Peptides by High Density Resting B Cells

2002 ◽  
Vol 168 (8) ◽  
pp. 3865-3873 ◽  
Author(s):  
Christopher M. Snyder ◽  
Xianghua Zhang ◽  
Lawrence J. Wysocki
Keyword(s):  
B Cells ◽  
B Cell ◽  
Cell Receptor ◽  
Class Ii ◽  
B Cell Receptor ◽  
High Density ◽  
Class Ii Mhc ◽  
Mhc Presentation

scholarly journals Distinct Intracellular Compartments Involved in Invariant Chain Degradation and Antigenic Peptide Loading of Major Histocompatibility Complex (MHC) Class II Molecules

1997 ◽  
Vol 139 (6) ◽  
pp. 1433-1446 ◽  
Author(s):  
Giorgio Ferrari ◽  
Andrew M. Knight ◽  
Colin Watts ◽  
Jean Pieters
Keyword(s):  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Human Leukocyte ◽  
Subcellular Location ◽  
Class Ii ◽  
Invariant Chain ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Peptide Loading ◽  
Mhc Class Ii Molecules

Major histocompatibility complex (MHC) class II molecules are transported to intracellular MHC class II compartments via a transient association with the invariant chain (Ii). After removal of the invariant chain, peptides can be loaded onto class II molecules, a process catalyzed by human leukocyte antigen-DM (HLA-DM) molecules. Here we show that MHC class II compartments consist of two physically and functionally distinct organelles. Newly synthesized MHC class II/Ii complexes were targeted to endocytic organelles lacking HLA-DM molecules, where Ii degradation occurred. From these organelles, class II molecules were transported to a distinct organelle containing HLA-DM, in which peptides were loaded onto class II molecules. This latter organelle was not directly accessible via fluid phase endocytosis, suggesting that it is not part of the endosomal pathway. Uptake via antigen-specific membrane immunoglobulin resulted however in small amounts of antigen in the HLA-DM positive organelles. From this peptide-loading compartment, class II–peptide complexes were transported to the plasma membrane, in part after transit through endocytic organelles. The existence of two separate compartments, one involved in Ii removal and the other functioning in HLA-DM–dependent peptide loading of class II molecules, may contribute to the efficiency of antigen presentation by the selective recruitment of peptide-receptive MHC class II molecules and HLA-DM to the same subcellular location.

scholarly journals Binding sites for bacterial and endogenous retroviral superantigens can be dissociated on major histocompatibility complex class II molecules.

1994 ◽  
Vol 179 (3) ◽  
pp. 1029-1034 ◽  
Author(s):  
J Thibodeau ◽  
N Labrecque ◽  
F Denis ◽  
B T Huber ◽  
R P Sékaly
Keyword(s):  
T Cells ◽  
Major Histocompatibility Complex ◽  
Mhc Class Ii ◽  
Binding Sites ◽  
Cell Receptor ◽  
Class Ii ◽  
Bacterial Toxins ◽  
Major Histocompatibility ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Molecules

Bacterial and retroviral superantigens (SAGs) interact with major histocompatibility complex (MHC) class II molecules and stimulate T cells upon binding to the V beta portion of the T cell receptor. Whereas both types of molecules exert similar effects on T cells, they have very different primary structures. Amino acids critical for the binding of bacterial toxins to class II molecules have been identified but little is known of the molecular interactions between class II and retroviral SAGs. To determine whether both types of superantigens interact with the same regions of MHC class II molecules, we have generated mutant HLA-DR molecules which have lost the capacity to bind three bacterial toxins (Staphylococcus aureus enterotoxin A [SEA], S. aureus enterotoxin B [SEB], and toxic shock syndrome toxin 1 [TSST-1]). Cells expressing these mutated class II molecules efficiently presented two retroviral SAGs (Mtv-9 and Mtv-7) to T cells while they were unable to present the bacterial SAGs. These results demonstrate that the binding sites for both types of SAGs can be dissociated.

scholarly journals The protein tyrosine kinase p56lck regulates cell adhesion mediated by CD4 and major histocompatibility complex class II proteins.

1994 ◽  
Vol 180 (5) ◽  
pp. 1729-1739 ◽  
Author(s):  
M S Kinch ◽  
A Sanfridson ◽  
C Doyle
Keyword(s):  
Cell Adhesion ◽  
B Cells ◽  
Tyrosine Kinase ◽  
Mhc Class Ii ◽  
Kinase Activity ◽  
Class Ii ◽  
Wild Type ◽  
Tyrosine Kinase Activity ◽  
Histocompatibility Complex ◽  
Mhc Class Ii Molecules

The CD4 protein is expressed on a subset of human T lymphocytes that recognize antigen in the context of major histocompatibility complex (MHC) class II molecules. Using Chinese hamster ovary (CHO) cells expressing human CD4, we have previously demonstrated that the CD4 protein can mediate cell adhesion by direct interaction with MHC class II molecules. In T lymphocytes, CD4 can also function as a signaling molecule, presumably through its intracellular association with p56lck, a member of the src family of protein tyrosine kinases. In the present report, we show that p56lck can affect cell adhesion mediated by CD4 and MHC class II molecules. The expression of wild-type p56lck in CHO-CD4 cells augments the binding of MHC class II+ B cells, whereas the expression of a mutant p56lck protein with elevated tyrosine kinase activity results in decreased binding of MHC class II+ B cells. Using site-specific mutants of p56lck, we demonstrate that the both the enzymatic activity of p56lck and its association with CD4 are required for this effect on CD4/MHC class II adhesion. Further, the binding of MHC class II+ B cells induces CD4 at the cell surface to become organized into structures resembling adhesions-type junctions. Both wild-type and mutant forms of p56lck influence CD4-mediated adhesion by regulating the formation of these structures. The wild-type lck protein enhances CD4/MHC class II adhesion by augmenting the formation of CD4-associated adherens junctions whereas the elevated tyrosine kinase activity of the mutant p56lck decreases CD4-mediated cell adhesion by preventing the formation of these structures.

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