Influence of membrane Ig receptor density and affinity on B cell signaling by antigen. Implications for affinity maturation.

George, Julia M.; Penner, S. J.; Weber, Johann; Berry, Jody D.; Claflin, J L

doi:10.4049/jimmunol.151.11.5955

Cited by 23 publications

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Immunization with immune complex alters the repertoire of antigen‐reactive B cells in the germinal centers

1997

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The differentiation of memory B cells in germinal centers (GC) is selectively enhanced upon administration of antigen-antibody complexes. To characterize the repertoire of this response, we examined the rearranged immunoglobulin heavy chain variable (V(H)) genes from mouse splenic GC after a single immunization with either antigen, nitrophenyl (NP) hapten coupled to keyhole limpet hemocyanin, or with a preformed complex of antigen with a monoclonal anti-NP antibody of gamma1 isotype. Among antigen-immunized mice, NP-reactive GC B cell populations in the antigen-induced GC consisted mostly of cells expressing the canonical V186.2 gene which contained, on average, 0.8 point mutations/V(H) gene by day 8 after immunization. These results are indicative of the beginning of somatic hypermutation and consistent with previously published analyses of NP antigen-driven GC. In contrast, the NP-specific B cells in GC that were elicited by administration of immune complex represented a heterogeneous cell population expressing nine different germ-line segments of the V186.2/V3 (J558) gene family, i.e. V23, V24.8, C1H4, V3, CH10, V165.1, V102, V671.5 and V186.2. Moreover, the average frequency of mutations in these genes was 1.7, reaching up to 4 mutations/V(H) in some GC. Administration of the antigen NP in complex with specific antibody apparently alters the process of interclonal competition in the GC and results in loss of dominance by V186.2+ cells and nearly stochastic representation of diverse clonotypes. These results suggest an important feedback regulation of the B cell repertoire by antibody and indicate a role for immune complexes in the activation of somatic hypermutation.

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Immunization with immune complex alters the repertoire of antigen‐reactive B cells in the germinal centers

1997

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Toward Quantitative Simulation of Germinal Center Dynamics: Biological and Modeling Insights from Experimental Validation

Kleinstein

Singh

2001

Journal of Theoretical Biology

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Signaling Chain Homooligomerization (SCHOOL) Model

Sigalov

Advances in Experimental Medicine and Biology

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Multichain immune recognitionreceptors (MIRRs) represent a family of surfacereceptors expressed on different cells of the hematopoietic system and function to transduce signals leading to a variety of biologic responses. The most intriguing and distinct structural feature ofMIRR family members is that extracellular recognition domains and intracellular signaling domains are located on separate subunits. The biochemical cascades triggered by MIRRs are understood in significant detail, however, the mechanism by which extracellular ligand binding initiates intracellular signal transduction processes is not clear and no model fully explains how MIRR signaling commences. In this Chapter, I describe a novel mechanistic model of MIRR-mediated signal transduction, the signaling chain homooligomerization (SCHOOL) model. The basic concept of this model assumes that the structural similarity of the MIRRs provides the basis for the similarity in the mechanisms ofMIRR-mediated transmembrane signaling. Within the SCHOOL model, MIRR triggering is considered to be a result of the ligand-induced interplay between (1) intrareceptor transmembrane interactions between MIRR recognition and signaling subunits that stabilize and maintain receptor integrity and (2) interreceptor homointeractions between MIRR signaling subunits that lead to the formation of oligomeric signaling structures, thus triggering the receptors and initiating the signaling cascade. Thus, the SCHOOL model is based on specific protein-protein interactions--biochemical processes that can be influenced and controlled. In this context, this plausible and easily testable model is fundamentally different from those previously suggested for particular MIRRs and has several important advantages. The basic principles oftransmembrane signaling learned from the SCHOOL model may be used in different fields of immunology and cell biology to describe, explain and predict immunological phenomena and processes mediated by structurally related but functionally different membrane receptors. Important applications of the SCHOOL model in clinical immunology, molecular pharmacology and virology are described in the Chapters 20 and 22 of this book.

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Influence of membrane Ig receptor density and affinity on B cell signaling by antigen. Implications for affinity maturation.

Cited by 23 publications

References 0 publications

Immunization with immune complex alters the repertoire of antigen‐reactive B cells in the germinal centers

Immunization with immune complex alters the repertoire of antigen‐reactive B cells in the germinal centers

Toward Quantitative Simulation of Germinal Center Dynamics: Biological and Modeling Insights from Experimental Validation

Signaling Chain Homooligomerization (SCHOOL) Model

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