B-Cell Generation, Activation and Differentiation - III


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B-Cell Generation, Activation and Differentiation - III
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The Humoral Response – I
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The Humoral Response – II
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Germinal Centers and Antigen Induced B-Cell Differentiation - I
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Germinal Centers and Antigen Induced B-Cell Differentiation - II
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Regulation of B-Cell Development and Immune Effector Response

Lecture´s Description

The Humoral Response - I

This Sqadia video highlights about B- cells generation, activation and differentiation. The kinetics and other characteristics of the humoral response differ considerably depending on whether the humoral response results from activation of naive lymphocytes (primary response) or memory lymphocytes (secondary response). The memory B cells formed during a primary response stop dividing and enter the G0 phase of the cell cycle. These cells have variable life spans, with some persisting for the life of the individual. The capacity to develop a secondary humoral response. The secondary response is also characterized by secretion of antibody with a higher affinity for the antigen, and isotypes other than IgM predominate. The existence of long-lived memory B cells accounts for a phenomenon called “original antigenic sin,” which was first observed when the antibody response to influenza vaccines was monitored in adults.

The Humoral Response – II

T Helper cells play a critical role in the humoral response to hapten-carrier conjugates. Hapten carrier conjugate used for the primary immunization. If the secondary immunization was with the same hapten but conjugated to a different, unrelated carrier, no secondary anti hapten response occurred. This phenomenon, called the carrier effect, could be circumvented by priming the animal separately with the unrelated carrier. In vivo activation and differentiation of B cells occurs in defined anatomic sites whose structure places certain restrictions on the kinds of cellular interactions that can take place. Activated B cells (together with some activated TH cells) may migrate towards the center of the secondary follicle, forming a germinal center.

Germinal Centers and Antigen Induced B-Cell Differentiation - I

Germinal centers arise within 7–10 days after initial exposure to a thymus-dependent antigen. During the first stage of germinal-center formation, activated B cells undergo intense proliferation. These proliferating B cells, known as centroblasts, appear in human germinal centers as a well-defined dark zone. The average affinity of the antibodies produced during the course of the humoral response increases remarkably during the process of affinity maturation. Monitoring of antibody genes during an immune response shows that extensive mutation of the Ig genes that respond to the infection takes place in B cells within germinal centers. A direct demonstration that germinal centers are the sites of somatic hypermutation comes from the work of G. Kelsoe and his colleagues.

Germinal Centers and Antigen Induced B-Cell Differentiation - II

Somatic hypermutation of heavy and light-chain variable region genes occurs when centroblasts proliferate in the dark zone of the germinal center. Selection takes place in the light zone, among the nondividing centrocyte population. The most important factor influencing selection is the ability of the membrane Ig molecules on the centrocyte to recognize and bind antigen displayed by follicular dendritic cells (FDCs). Antibodies perform two important activities: the specific binding to an antigen, which is determined by the VH and VL domains; and participation in various biological effector functions, which is determined by the isotype of the heavy chain constant domain. After B cells are selected in the germinal center for those bearing high-affinity mIg for antigen displayed on follicular dendritic cells, some B cells differentiate into plasma cells and others become memory B cells.

Regulation of B-Cell Development and Immune Effector Response

A number of transcription factors that regulate expression of various gene products at different stages of B-cell development have been identified. The immunologic history of an animal influences the quality and quantity of its immune response. A naive animal responds to antigen challenges very differently from a previously primed animal. Previous encounter with an antigen may have rendered the animal tolerant to the antigen or may have resulted in the formation of memory cells. Like many biochemical reactants, antibody exerts feedback inhibition on its own production. Because of antibody mediated suppression, certain vaccines are not administered to infants before the age of 1 year.The level of naturally acquired maternal IgG, which the fetus acquires by transplacental transfer, remains high for about 6 months after birth. Only the high-affinity antigen-reactive cells can compete successfully with the passively administered antibody for the available antigen.

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