The Effect of B Cell Receptor Signaling on Antigen Endocytosis and Processing

McGovern, Erica M.; Moquin, Amy; Caballero, Adriana; Drake, James R.

doi:10.1081/imm-120030733

Cited by 13 publications

(21 citation statements)

References 20 publications

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“…Finally, prestimulation of nontransgenic B cells with goat anti-F(abЈ) 2 Ab could not rescue the loss of B cells, thus confirming our earlier results with the C4H3 mAb in resting B cells (Fig. 2, A and B) and our data on the inability of BCR signaling to alter fluid phase uptake and processing of HEL (16).…”

Section: Differential Effect Of Ligation Of Type I and Ii Complexes Fsupporting

confidence: 81%

“…2B), suggesting that the depletion resulting from ligation of type II complexes is dominant over the lack of depletion observed following ligation of type I complexes. Thus, not only does BCR signaling fail to alter processing of fluid phase Ag (16), but also our data suggest that the signaling function of the type II complex that leads to B cell loss is similarly not significantly affected.…”

Section: Differential Effect Of Ab Ligation Of Type I and Ii Complexementioning

confidence: 67%

“…The processing of HEL involves the generation of HEL 46 -61 -I-A k complexes in late endosomal compartments (17,18). Both 3A9 T cells and the C4H3 mAb recognize the peptide-MHC complex (16,31). Using a B cell hybridoma, four HEL peptides varying in length, but containing the core dominant sequence 52-61, were found complexed to I-A k , in addition to one peptide, HEL 48 -60 (32).…”

Section: Discussionmentioning

confidence: 99%

“…Importantly, while saturation of the first phase is directly related to saturation of the BCR (data not shown), the second phase of Ag processing is not saturated with Ag concentration as high as 1 mM HEL. It should be noted that BCR signaling fails to alter the efficiency of fluid phase processing (16). Furthermore, in this system, the generation of HEL 46 -61 -I-A k complexes via both fluid phase and BCR-mediated processing occurs exclusively via newly synthesized CII molecules (17, 18) (also our unpublished data).…”

Section: Quantification Of B:t Cell Conjugates By Flow Cytometrymentioning

confidence: 99%

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The Pathway of Antigen Uptake and Processing Dictates MHC Class II-Mediated B Cell Survival and Activation

Nashar

Drake

2005

The Journal of Immunology

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The influence of the pathway of Ag uptake and processing on MHC class II (CII)-mediated B cell function is unknown. In this study, we investigate in resting and activated (via the BCR or CD40) B cells the biological properties of CII-peptide complexes (CII-peptide) generated by either the BCR-mediated Ag processing (type I complex) or fluid phase Ag processing (type II complex). Compared with type I complex, ligation of type II complex by either specific Ab or the TCR in Ag-presenting assay results in significant decreases in B cell survival rate (50–100%) and expression levels of CII, CD86, and CD54. Loss of B cells following ligation of type II complex occurs in the presence of a comparatively good level of specific CD4+ T cell division, indicating that B cell loss is a late event following T cell stimulation. Comparative analysis of T and B cell conjugates after Ab ligation of type I or II complex reveals decreased efficiency of the latter in forming conjugates. Neither initial differential levels of CII and other studied surface markers, B cell type inherent differences, BCR signaling, T cell proliferation, nor initial density of CII-peptide complexes could explain the T cell-induced B cell loss. We propose that the context in which CII-peptide complexes are present in the membrane following BCR uptake and processing leads to B cell survival. Thus, appropriate targeting of Ag ensures generation of relevant immune responses.

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Section: Differential Effect Of Ligation Of Type I and Ii Complexes Fsupporting

confidence: 81%

Section: Differential Effect Of Ab Ligation Of Type I and Ii Complexementioning

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Section: Quantification Of B:t Cell Conjugates By Flow Cytometrymentioning

confidence: 99%

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The Pathway of Antigen Uptake and Processing Dictates MHC Class II-Mediated B Cell Survival and Activation

Nashar

Drake

2005

The Journal of Immunology

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“…In addition to facilitating Ag internalization, BCR-induced kinase cascades may be involved in intracellular targeting of BCR-Ag complexes to mature MHC-II loading compartments (17). However, some studies suggest that many of the fundamental endocytic processes required for Ag presentation can occur via phosphorylation-independent BCR endocytosis mechanisms (18,19). We have previously found that cytoskeletal rearrangement processes within dendritic cells are critical for efficient formation of immune synapses with T cells (20); however, it is unknown whether BCR-induced cytoskeletal rearrangements may affect the ability of Ag-bearing B cells to form functional synapses with T cells.…”

mentioning

confidence: 99%

Bam32/DAPP1 Promotes B Cell Adhesion and Formation of Polarized Conjugates with T Cells

Al‐Alwan¹,

Hou²,

Zhang

et al. 2010

The Journal of Immunology

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B cell Ag receptors function in both signaling activation of Ag-specific cells and in collecting specific Ag for presentation to T lymphocytes. Signaling via PI3K is required for BCR-mediated activation and Ag presentation functions; however, the relevant downstream targets of PI3K in B cells are incompletely defined. In this study, we have investigated the roles of the PI3K effector molecule Bam32/DAPP1 in BCR signaling and BCR-mediated Ag presentation functions. In mouse primary B cells, Bam32 was required for efficient activation of the GTPase Rac1 and downstream signaling to JNK, but not activation of BLNK, phospholipase C γ2, or calcium responses. Consistent with a role of this adaptor in Rac-mediated cytoskeletal rearrangement, Bam32 was required for BCR-induced cell adhesion and spreading responses on ICAM-1 or fibronectin-coated surfaces. The function of Bam32 in promoting Rac activation and adhesion required tyrosine 139, a known site of phosphorylation by Lyn kinase. After BCR crosslinking by Ag, Bam32-deficient B cells are able to carry out the initial steps of Ag endocytosis and processing, but show diminished ability to form Ag-specific conjugates with T cells and polarize F-actin at the B-T interface. As a result, Bam32-deficient B cells were unable to efficiently activate Ag-specific T cells. Together, these results indicate that Bam32 serves to integrate PI3K and Src kinase signaling to promote Rac-dependent B cell adhesive interactions important for Ag presentation function.

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Diversity and Epitope Spreading of Anti–RNA Polymerase III Antibodies in Systemic Sclerosis: A Potential Biomarker for Skin and Lung Involvement

Kotani,

Matsuda,

Yamaguchi

et al. 2024

Arthritis & Rheumatology

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ObjectiveEpitope spreading (ES), involving autoantibodies, plays a crucial role in the development and persistence of autoimmune reactions in various autoimmune diseases. This study aimed to investigate the relationship between ES of anti–RNA polymerase III (RNAP III) antibodies (ARAs) and the clinical manifestations of systemic sclerosis (SSc).MethodsWe investigated whether intermolecular ES occurs in the subunits of the RNAP III complex and whether intramolecular ES targets the major antigen, RNA polymerase III subunit A (RPC1), in patients with SSc. To achieve this, we synthesized 17 full‐length subunit proteins of the RNAP III complex and 5 truncated forms of RPC1 in vitro using a wheat germ cell‐free translation system. Subsequently, we prepared antigen‐binding plates and measured autoantibodies in the serum of patients with SSc.ResultsAutoantibodies against different RNAP III complex subunits were found in patients who were ARA‐positive with SSc. The intermolecular ES indicators significantly correlated with the modified Rodnan skin thickness score (mRSS) and surfactant protein‐D, a biomarker of interstitial lung disease. However, the extent of disease on high‐resolution computed tomography or pulmonary function tests did not show any significant correlation. Intramolecular ES indicator against RPC1 were significantly correlated with mRSS and renal crisis. Furthermore, longitudinal assessment of ES in RNAP III complex subunits correlated with mRSS and exhibited potential as a disease activity biomarker.ConclusionOur findings indicate a correlation between ES levels and the severity of skin sclerosis or the risk of other complications in SSc. This study suggests that measuring ES in SSc serves as a novel biomarker for disease activity.image

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The Effect of B Cell Receptor Signaling on Antigen Endocytosis and Processing

Cited by 13 publications

References 20 publications

The Pathway of Antigen Uptake and Processing Dictates MHC Class II-Mediated B Cell Survival and Activation

The Pathway of Antigen Uptake and Processing Dictates MHC Class II-Mediated B Cell Survival and Activation

Bam32/DAPP1 Promotes B Cell Adhesion and Formation of Polarized Conjugates with T Cells

Diversity and Epitope Spreading of Anti–RNA Polymerase III Antibodies in Systemic Sclerosis: A Potential Biomarker for Skin and Lung Involvement

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