Sites of B-cell activation in vivo

doi:10.1016/0952-7915(93)90062-W

Current Opinion in Immunology

Volume 5, Issue 3, June 1993, Pages 418-422

https://doi.org/10.1016/0952-7915(93)90062-W Get rights and content

Abstract

Novel techniques have made possible in situ analyses of the lymphocyte populations responding to antigen. In the spleen, antigen-specific T and B cells are first observed in the periarteriolar lymphoid sheath. Following conjugate formation between specific T and B lymphocytes, B-cell proliferation and differentiation takes place in two distinct sites, the periarteriolar lymphoid sheath-associated foci and germinal centers.

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Guidance of B Cells by the Orphan G Protein-Coupled Receptor EBI2 Shapes Humoral Immune Responses
2009, Immunity
Citation Excerpt :
Dynamic changes in lymphocyte localization are fundamental to the rapid and efficient production of protective antibodies. Antibody responses are initiated by the relocalization of antigen-engaged B cells to the B zone-T zone (B-T) boundary where cognate interactions with T cells drive initial B cell proliferation (Kelsoe and Zheng, 1993; Okada and Cyster, 2006). Proliferating B cell blasts subsequently proceed down one of two independent pathways of migration and differentiation (Jacob et al., 1991; Liu et al., 1991).
Humoral immunity depends on both rapid and long-term antibody production against invading pathogens. This is achieved by the generation of spatially distinct extrafollicular plasmablast and follicular germinal center (GC) B cell populations, but the signals that guide responding B cells to these alternative compartments have not been fully elucidated. Here, we show that expression of the orphan G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2, also known as GPR183) by activated B cells was essential for their movement to extrafollicular sites and induction of early plasmablast responses. Conversely, downregulation of EBI2 enabled B cells to access the center of follicles and promoted efficient GC formation. EBI2 therefore provides a previously uncharacterized dimension to B cell migration that is crucial for coordinating rapid versus long-term antibody responses.
Initial Clonal Expansion of Germinal Center B Cells Takes Place at the Perimeter of Follicles
2009, Immunity
Citation Excerpt :
During T cell dependent (TD) immune responses, B cells undergo proliferation, differentiation, and selection in the microenvironment of the germinal center (GC), thereby leading to the formation of the memory B cell compartment. According to many models, the GC response takes place in a series of discrete stages (Kelsoe and Zheng, 1993; MacLennan, 1994; Liu and Arpin, 1997; Camacho et al., 1998). After their antigen receptors (BCRs) engage antigen, follicular B cells migrate to near the border of T zones and undergo cognate interaction with helper T cells.
Current models of the germinal center (GC) response propose that after stimulation at the edges of T cell zones, pre-GC B cells directly migrate to the center of follicles and proliferate to form GCs. We followed the interrelationship of proliferation, differentiation, and microenvironmental locale in populations of pre-GC B cells responding to antigen. In contrast to the predictions of current models, after accumulation at the T-B interface, these cells appeared at the perimeter of follicles adjacent to the marginal zone. There, they rapidly proliferated for several days but underwent no V gene hypermutation and little heavy-chain class switching. Their chemokine receptor expression pattern indicated that these cells were sessile, yet they had begun to acquire many phenotypic characteristics of GC B cells. The expanded clones were subsequently observed in the center of follicles, suggesting that GCs are created by coalescence of B cells from this follicular perimeter response.
NORMAL AND IMPAIRED IMMUNOLOGIC RESPONSES TO INFECTION
2009, Feigin and Cherry's Textbook of Pediatric Infectious Diseases, Sixth Edition
IgA B cell development
2005, Mucosal Immunology, Two-Volume Set
Transient suppression of IgG1 with IL-6 over-expression in immunized TCR-transgenic mice
2004, Immunology Letters
Helper T cell-derived cytokines play a pivotal role in the production of antigen-specific IgG antibody by B cells. In order to examine the in vivo effect of massive activation of helper T cells on the production of specific antibodies, ovalbumin (OVA)-specific TCR transgenic mice (OVA23-3) were immunized with OVA and serum levels of antigen-specific antibodies were measured. As a result, a great enhancement of antigen-specific IgM secretion and delay of IgG secretion were observed while the T cells produced sufficient Th2 cytokines. Immediately after OVA-immunization, marked increase of serum IL-6 was noted, which was followed by a transient increase of antibody forming cells. Both in vivo and in vitro experiments demonstrated that excess amount of IL-6 enhanced IgM production by activated B cells while suppressing IgG production. These results suggest that overproduction of IL-6 in the early stages of the primary immunization promotes development of IgM producing cells and causes the delay of IgG1 secretion.
Immune reactions
2003, NeuroImmune Biology
Under physiological conditions the immune system provides continuous defense against infectious agents and cancer, and is part of the homeostatic neuroimmune regulatory circuit that coordinates the normal function of the entire organism. The immune system is a local and mobile defense and regulatory system that has enormous capacity to deliver defense and regulatory molecules to sites that are in need. Every organ and tissue possesses stromal lymphoid elements that intervene locally to control autoimmune reactions, inflammation, and in general, participate in the physiological processes, as it is becoming obvious from recent investigations. Adaptive cell mediated and humoral immunity and immunological memory are reactions exerted by T and B lymphocytes in concert with members of the leukocyte series. Innate host defense relies on non-immune mechanisms and on specialized immune cells, such as natural killer cells, γδT lymphocytes and CD5⁺ B cells. The alternately activated complement system and of T and B lymphocytes are also part of the natural immune system. The natural immune system relies on germ-line coded receptors that recognizes evolutionarily highly preserved homologous epitopes (homotopes) on microbes and also on self components. Finally, immunocytes are present in various tissues and organs and participate in the normal physiological regulation in addition to providing defense.
Cell-to-cell interactions by the antigen receptor and of MHC molecules and by other adhesion molecules are fundamental to immune activation as well as to stromal regulation. Cytokines and complement fine-tune this regulatory system. In addition, the immune system interacts with the neural elements and mediators, parenchymal and stromal cells as part of the local gerulatory circuits that govern the organ/tissue under physiological circumstances.

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Current Opinion in Immunology

Abstract

References (31)

In situ Studies of the Primary Immune Response to (4-hydroxy-3-nitrophenyl)acetyl II. A Common Clonal Origin for Periarteriolar Lymphoid Sheath-associated Foci and Germinal Centers

J Exp Med

Predominant Use of a Va Gene Segment in Mouse T-cell Receptors for Cytochrome c

Nature

Germinal Centres and the Origin of the B Cell System. II. Germinal Centres in the Rabbit Spleen and Popliteal Lymph Nodes

Immunology

in Situ Studies of the Primary Response to (4-hydroxy-3-nitrophenyl)acetyl. I. The Architecture and Dynamics of Responding Cell Populations

J Exp Med

Studies of Specific B Cell Activation in Primary and Secondary Responses to T Cell-dependent and T Cell-independent Antigens

Eur J Immunol

Peanut Lectin-binding Properties of Germinal Centers in Mouse Lymphoid Tissue

Nature

Interaction of Peanut Agglutinin with Normal Human Lymphocytes and with Leukemic Cells

The Maintenance and Regulation of the Humoral Immune Response: Persisting Antigen and the Role of Follicular Antigen-binding Dendritic Cells as Accessory Cells

Immunol Rev

A Novel in Vivo Follicular dentritic Cell-dependent Iccosome-mediated Mechanism for Delivery of Antigen to Antigen-processing Cells

J Immunol

Clustering of Dendritic Cells Helper T Lymphocytes, and Histocompatible B Cells During Primary Antibody Responses _Vitro

J Exp Med

Mouse Epidermal Ia Molecules Have a Bone Marrow Origin

Nature

Immunohistochemical Characterizition of Cells Involved in Dermatopathic Lymphadenopathy

J Pathol

Myeloid Antigens: New and Previously Defined Clusters

Reactivity of Myeloid Monoclonal Antibodies with Human Dendritic Cells

Activation of Human B Cells Mediated Through Two Distint Cell Surface Differentiation Antigens. Bp35 and Bp50

Cited by (62)

Guidance of B Cells by the Orphan G Protein-Coupled Receptor EBI2 Shapes Humoral Immune Responses

Initial Clonal Expansion of Germinal Center B Cells Takes Place at the Perimeter of Follicles

NORMAL AND IMPAIRED IMMUNOLOGIC RESPONSES TO INFECTION

IgA B cell development

Transient suppression of IgG1 with IL-6 over-expression in immunized TCR-transgenic mice

Immune reactions

Sites of B-cell activation in vivo

Abstract

J Exp Med

Nature

Germinal Centres and the Origin of the B Cell System. II. Germinal Centres in the Rabbit Spleen and Popliteal Lymph Nodes

Immunology

in Situ Studies of the Primary Response to (4-hydroxy-3-nitrophenyl)acetyl. I. The Architecture and Dynamics of Responding Cell Populations

J Exp Med

Studies of Specific B Cell Activation in Primary and Secondary Responses to T Cell-dependent and T Cell-independent Antigens

Eur J Immunol

Peanut Lectin-binding Properties of Germinal Centers in Mouse Lymphoid Tissue

Nature

Interaction of Peanut Agglutinin with Normal Human Lymphocytes and with Leukemic Cells

The Maintenance and Regulation of the Humoral Immune Response: Persisting Antigen and the Role of Follicular Antigen-binding Dendritic Cells as Accessory Cells

Immunol Rev

A Novel in Vivo Follicular dentritic Cell-dependent Iccosome-mediated Mechanism for Delivery of Antigen to Antigen-processing Cells

J Immunol

Clustering of Dendritic Cells Helper T Lymphocytes, and Histocompatible B Cells During Primary Antibody Responses Vitro

J Exp Med

Mouse Epidermal Ia Molecules Have a Bone Marrow Origin

Nature

Immunohistochemical Characterizition of Cells Involved in Dermatopathic Lymphadenopathy

J Pathol

Myeloid Antigens: New and Previously Defined Clusters

Reactivity of Myeloid Monoclonal Antibodies with Human Dendritic Cells

Activation of Human B Cells Mediated Through Two Distint Cell Surface Differentiation Antigens. Bp35 and Bp50

Clustering of Dendritic Cells Helper T Lymphocytes, and Histocompatible B Cells During Primary Antibody Responses _Vitro