Crystal structure of IgE bound to its B-cell receptor CD23 reveals a mechanism of reciprocal allosteric inhibition with high affinity receptor Fc RI

B cells produce high-affinity immunoglobulins (Igs), or antibodies, to eliminate foreign pathogens. Mature, naïve B cells expressing an antigen-specific cell surface Ig, or B cell receptor (BCR), are directed toward either an extrafollicular (EF) or germinal center (GC) response upon antigen binding. B cell interactions with CD4+ pre-T follicular helper (pre-Tfh) cells at the T-B border and effector Tfh cells in the B cell follicle and GC control B cell development in response to antigen. Here, we review recent studies demonstrating the role of B cell receptor (BCR) affinity in modulating T-B interactions and the subsequent differentiation of B cells in the EF and GC response. Overall, these studies demonstrate that B cells expressing high affinity BCRs preferentially differentiate into antibody secreting cells (ASCs) while those expressing low affinity BCRs undergo further affinity maturation or differentiate into memory B cells (MBCs).

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Early lymphocyte expansion is severely impaired in interleukin 7 receptor-deficient mice.

Journal of Experimental Medicine ◽

10.1084/jem.180.5.1955 ◽

1994 ◽

Vol 180 (5) ◽

pp. 1955-1960 ◽

Cited By ~ 1111

Author(s):

J J Peschon ◽

P J Morrissey ◽

K H Grabstein ◽

F J Ramsdell ◽

E Maraskovsky ◽

...

Keyword(s):

T Cell ◽

Developmental Stages ◽

Receptor Gene ◽

Critical Role ◽

Cell Receptor ◽

High Affinity ◽

Interleukin 7 ◽

High Affinity Receptor ◽

Affinity Receptor ◽

Deficient Mice

Interleukin 7 (IL-7) stimulates the proliferation of B cell progenitors, thymocytes, and mature T cells through an interaction with a high affinity receptor (IL-7R) belonging to the hematopoietin receptor superfamily. We have further addressed the role of IL-7 and its receptor during B and T cell development by generating mice genetically deficient in IL-7R. Mutant mice display a profound reduction in thymic and peripheral lymphoid cellularity. Analyses of lymphoid progenitor populations in IL-7R-deficient mice define precisely those developmental stages affected by the mutation and reveal a critical role for IL-7R during early lymphoid development. Significantly, these studies indicate that the phase of thymocyte expansion occurring before the onset of T cell receptor gene rearrangement is critically dependent upon, and mediated by the high affinity receptor for IL-7.

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Identification of a novel stereotypic IGHV4-59/IGHJ5-encoded B-cell receptor subset expressed by various B-cell lymphomas with high affinity rheumatoid factor activity

Haematologica ◽

10.3324/haematol.2015.139626 ◽

2016 ◽

Vol 101 (5) ◽

pp. e200-e203 ◽

Cited By ~ 10

Author(s):

R. J. Bende ◽

J. Janssen ◽

T. A. M. Wormhoudt ◽

K. Wagner ◽

J. E. J. Guikema ◽

...

Keyword(s):

B Cell ◽

Rheumatoid Factor ◽

Cell Receptor ◽

B Cell Receptor ◽

Factor Activity ◽

B Cell Lymphomas ◽

High Affinity ◽

Rheumatoid Factor Activity

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Peripheral B cell receptor editing may promote the production of high-affinity autoantibodies in CD22-deficient mice

European Journal of Immunology ◽

10.1002/eji.200636190 ◽

2006 ◽

Vol 36 (10) ◽

pp. 2755-2767 ◽

Cited By ~ 11

Author(s):

Yuval Yarkoni ◽

Ruth Fischel ◽

Inbal Kat ◽

Nurit Yachimovich-Cohen ◽

Dan Eilat

Keyword(s):

B Cell ◽

Cell Receptor ◽

B Cell Receptor ◽

Receptor Editing ◽

High Affinity ◽

Deficient Mice

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The distinctive germinal center phase of IgE+ B lymphocytes limits their contribution to the classical memory response

Journal of Experimental Medicine ◽

10.1084/jem.20131539 ◽

2013 ◽

Vol 210 (12) ◽

pp. 2755-2771 ◽

Cited By ~ 71

Author(s):

Jin-Shu He ◽

Michael Meyer-Hermann ◽

Deng Xiangying ◽

Lim Yok Zuan ◽

Leigh Ann Jones ◽

...

Keyword(s):

Cell Differentiation ◽

B Cell ◽

Germinal Center ◽

Cell Receptor ◽

B Cell Receptor ◽

Comprehensive Model ◽

B Cell Differentiation ◽

Memory Response ◽

High Affinity ◽

Sequential Switching

The mechanisms involved in the maintenance of memory IgE responses are poorly understood, and the role played by germinal center (GC) IgE+ cells in memory responses is particularly unclear. IgE+ B cell differentiation is characterized by a transient GC phase, a bias toward the plasma cell (PC) fate, and dependence on sequential switching for the production of high-affinity IgE. We show here that IgE+ GC B cells are unfit to undergo the conventional GC differentiation program due to impaired B cell receptor function and increased apoptosis. IgE+ GC cells fail to populate the GC light zone and are unable to contribute to the memory and long-lived PC compartments. Furthermore, we demonstrate that direct and sequential switching are linked to distinct B cell differentiation fates: direct switching generates IgE+ GC cells, whereas sequential switching gives rise to IgE+ PCs. We propose a comprehensive model for the generation and memory of IgE responses.

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