期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 24, 页码 8345-8350出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0802968105
关键词
innate; B cell activation; antigen affinity
资金
- Cancer Research UK [C399/A2291] Funding Source: Medline
- Medical Research Council [G0501975, MC_U137884181, G0400421] Funding Source: Medline
- Wellcome Trust Funding Source: Medline
- Medical Research Council [G0400421, G0501975, MC_U137884181] Funding Source: researchfish
- MRC [G0400421, G0501975, MC_U137884181] Funding Source: UKRI
Highly regulated activation of B cells is required for the production of specific antibodies necessary to provide protection from pathogen infection. This process is initiated by specific recognition of antigen through the B cell receptor (BCR), leading to early intracellular signaling followed by the late recruitment of T cell help. In this study we demonstrate that specific BCR uptake of CD1d-restricted antigens represents an effective means of enhancing invariant natural killer T (iNKT)-dependent B cell responses in vivo. This mechanism is effective over a wide range of antigen affinities but depends on exceeding a tightly regulated avidity threshold necessary for BCR-mediated internalization and CD1d-dependent presentation of particulate antigenic lipid-Subsequently, iNKT cells provide the help required for stimulating B cell proliferation and differentiation. iNKT-stimulated B cells develop within extrafollicular foci and mediate the production of high titers of specific IgM and early class-switched antibodies. Thus, we have demonstrated that in response to particulate antigenic lipids iNKT cells are recruited for the assistance of B cell activation, resulting in the enhancement of specific antibody responses. We propose that such a mechanism may operate to potentiate adaptive immune responses against pathogens in vivo.
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