MHC Class II Antigen Processing in B Cells: Accelerated Intracellular Targeting of Antigens

Cheng, Paul C.; Steele, Carrie R.; Gu, Lin; Song, Wenxia; Pierce, Susan K.

doi:10.4049/jimmunol.162.12.7171

Cited by 64 publications

(1 citation statement)

References 42 publications

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“…Reduced survival at 48 h was even more dramatic ( Supplementary Figure 3 ). Expression of activated markers in basal conditions was also explored, CD44 and I-A b were measured in B cells, both markers were observed in higher levels in Lrba -/- mice, indicating a basal activation status of these cells; both CD44 and MHC-II (I-A b ) are expressed in BCR-primed B cells, while I-A b , Figure 2C ( 39 , 40 ). Increased Ki67 expression was observed in Lrba -/- B cells indicating in situ B cell proliferation ( Supplementary Figure 1C ).…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-responsive beige-like anchor is involved in regulating NF-κB activation in B cells

Pérez-Pérez,

Fuentes-Pananá,

Flores-Hermenegildo

et al. 2024

Front. Immunol.

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IntroductionLipopolysaccharide-responsive and beige-like anchor (LRBA) is a scaffolding protein that interacts with proteins such as CTLA-4 and PKA, the importance of which has been determined in various cell types, including T regulatory cells, B cells, and renal cells. LRBA deficiency is associated with an inborn error in immunity characterized by immunodeficiency and autoimmunity. In addition to defects in T regulatory cells, patients with LRBA deficiency also exhibit B cell defects, such as reduced cell number, low memory B cells, hypogammaglobulinemia, impaired B cell proliferation, and increased autophagy. Although Lrba-/- mice do not exhibit the immunodeficiency observed in humans, responses to B cell receptors (BCR) in B cells have not been explored. Therefore, a murine model is for elucidating the mechanism of Lrba mechanism in B cells.AimTo compare and evaluate spleen-derived B cell responses to BCR crosslinking in C57BL6 Lrba-/- and Lrba+/+ mice.Materials and methodsSpleen-derived B cells were obtained from 8 to 12-week-old mice. Subpopulations were determined by immunostaining and flow cytometry. BCR crosslinking was assessed by the F(ab’)2 anti-μ chain. Activation, proliferation and viability assays were performed using flow cytometry and protein phosphorylation was evaluated by immunoblotting. The nuclear localization of p65 was determined using confocal microscopy. Nur77 expression was evaluated by Western blot.ResultsLrba-/- B cells showed an activated phenotype and a decreased proportion of transitional 1 B cells, and both proliferation and survival were affected after BCR crosslinking in the Lrba-/- mice. The NF-κB pathway exhibited a basal activation status of several components, resulting in increased activation of p50, p65, and IκBα, basal p50 activation was reduced by the Plcγ2 inhibitor U73122. BCR crosslinking in Lrba-/- B cells resulted in poor p50 phosphorylation and p65 nuclear localization. Increased levels of Nur77 were detected.DiscussionThese results indicate the importance of Lrba in controlling NF-κB activation driven by BCR. Basal activation of NF-κB could impact cellular processes, such as, activation, differentiation, proliferation, and maintenance of B cells after antigen encounter.

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Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide-responsive beige-like anchor is involved in regulating NF-κB activation in B cells

Pérez-Pérez,

Fuentes-Pananá,

Flores-Hermenegildo

et al. 2024

Front. Immunol.

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The influence of CD40 on the association of the B cell antigen receptor with lipid rafts in mature and immature cells

Malapati

Pierce

2001

Eur. J. Immunol.

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Cholesterol‐ and sphingolipid‐rich membrane microdomains termed lipid rafts appear to play a central role in B cell activation. In mature B cells, signaling through the B cell antigen receptor(BCR) is initiated from within rafts and leads to activation. In immature B cells, the BCR is excluded from rafts and signaling leads to apoptosis. CD40, a member of the tumor necrosis receptor family, is expressed by B cells throughout development and has been shown to influence the results of the engagement of antigen by the BCR in both mature B and immature B cells. Here evidence is provided that CD40 is excluded from the lipid rafts of both mature and immature B cells and remains excluded from rafts even after cross‐linking. Nevertheless, in mature B cells CD40 signaling influences the association of the BCR with rafts resulting in an increase in the amount of BCR that translocates into rafts following ligand binding and a subsequent acceleration of the movement of the BCR from rafts. In immature B cells, the cross‐linked BCR remains excluded from rafts in the presence of CD40 signaling, conditions under which BCR‐induced apoptosis is blocked. These results indicate that CD40 functions outside lipid rafts to influence raft‐dependent events in mature B cells and raft‐independent events in immature B cells.

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Specific role for cathepsin S in the generation of antigenic peptidesin vivo

Plüger

Boes

Alfonso³

et al. 2002

Eur. J. Immunol.

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To address the role of different proteases in degradation of antigen destined for MHC class II‐restricted presentation, we generated cathepsin‐deficient mice carrying a transgenic B cell receptor (BCR) specific for hen egg lysozyme (HEL). We demonstrate that degradation of HEL in B lymphocytes is highly processive and does not result in discrete processing intermediates. Moreover, degradation of HEL does not require initial unlocking of the antigen by any of the cathepsins tested. Using mass spectrometry and microsequencing, we show that all major cathepsins (CatS, CatL, CatB, and CatD) digest HEL in vitro with considerable redundancy, although some preferential cleavages are evident. These observations have a functional correlate: when triggered by cathepsin S‐deficient antigen‐presenting cells, T cells that recognize different HEL epitopes fail to present two HEL‐derived epitopes, while a third epitope is presented independently of the activity of cysteine proteases. We conclude that the proteolytic processing machinery is redundant, and that several proteases can substitute for each other to degrade a given antigen. However, a certain degree of proteolytic specificity is demonstrable for the generation of particular epitopes, notably by CatS.

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MHC Class II Antigen Processing in B Cells: Accelerated Intracellular Targeting of Antigens

Cited by 64 publications

References 42 publications

Lipopolysaccharide-responsive beige-like anchor is involved in regulating NF-κB activation in B cells

Lipopolysaccharide-responsive beige-like anchor is involved in regulating NF-κB activation in B cells

The influence of CD40 on the association of the B cell antigen receptor with lipid rafts in mature and immature cells

Specific role for cathepsin S in the generation of antigenic peptidesin vivo

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