B Cell Activation Fundamentals

Questions and Answers

Where do B cells get activated?

In the periphery, where they have antibodies on their surface to bind to antigens.

How do B cells get activated?

1st signal by the antigen, 2nd signal by the T cell, 3rd signal by cytokines from the T cell.

What type of interaction with T cells is required for T cell dependent B cell activation?

Cognate interaction.

What interaction is necessary with the T cell co-stimulatory molecule?

CD40L from T cell activates CD40 receptor on B cell. Signup and view all the answers

What are on B cell surfaces that help it become activated?

Antibodies, MHC molecule, CD40 receptor, complement receptors. Signup and view all the answers

How does the MHC molecule display an antigen to the T cell?

B cell endocytoses the antigen, breaks it up and puts the peptide pieces in the groove of MHC molecules. Signup and view all the answers

T cells can ONLY see an antigen from a B cell if?

Via MHC molecules. Signup and view all the answers

Explain the role of T cells in B cell activation in T dependent B-cell activation.

T cells provide signals needed to activate B cells and release cytokines to further activate B cells. Signup and view all the answers

What activates T cells and can be found on the surface of B cells when it has been bound with an antigen?

MHC. Signup and view all the answers

What is the first step in B cell activation?

Cross linking of BCRs. Signup and view all the answers

What delivers the signals of the antigen crosslinking with antibodies/BCRs?

Igalpha and Igbeta heterodimer with ITAMs. Signup and view all the answers

What are the 3 major intracellular signaling pathways ending in transcription factors that get triggered upon B cell activation?

NF-AT, NF-KB, AP-1. Signup and view all the answers

Describe the NF-AT ending intracellular signaling pathways triggered upon B cell activation.

PIP2 -> IP3 -> Ca2+ -calmodulin, calcineurin removes phosphate from NF-AT which goes to the nucleus as a transcription factor. Signup and view all the answers

Describe the NF-KB ending intracellular signaling pathways triggered upon B cell activation.

PIP2 -> DAG -> PKC phosphorylates IκB, leading to the release of NF-KB, allowing it to enter the nucleus. Signup and view all the answers

Describe the AP-1 ending intracellular signaling pathways triggered upon B cell activation.

Ras and Rac G proteins activate Mek/Mak kinase, leading to AP-1 entering the nucleus to activate cytokines. Signup and view all the answers

What is in the B cell coreceptor?

CD19, CD21 (CR2), CD81 (TAPA-1). Signup and view all the answers

How do B cell coreceptors amplify activation?

Bacteria/antigen binds to BCR, and its epitope binds to CR2/CD21 via C3d, delivering a strong signal to the B cell. Signup and view all the answers

Activation of resting B cells by T helper cells depends directly upon costimulatory interaction between?

CD40 and CD40L. Signup and view all the answers

What is negative signaling?

Every time a B cell is activated, it must be later turned off using the Fc receptor that inhibits Ig synthesis. Signup and view all the answers

Which B cell types actually secrete antibodies?

Plasma cells (B cell effectors). Signup and view all the answers

CD19 is usually a marker found on ALL types of B cells.

False Signup and view all the answers

What is special about CD81, an aspect of the B cell coreceptor?

It spans the transmembrane 4 times. Signup and view all the answers

Describe T (independent antigen) T1 vs T2.

TI-1 antigens activate B cells through BCR and TLR; TI-2 antigens require BCR clustering. Signup and view all the answers

Study Notes

B Cell Activation Overview

B cells become activated in the periphery, utilizing surface antibodies to bind to specific antigens.

Activation Signals

Initial activation requires two signals:
- First signal from the antigen binding to B cell receptors.
- Second signal from T cells, with potential cytokine assistance as a third signal.

Cognate Interaction

A cognate interaction between B cells and T cells is essential for T cell-dependent B cell activation.

Costimulatory Molecules

Activation interaction involves CD40L on T cells interacting with CD40 receptors on B cells.

Surface Markers and Activation

Key components on B cell surfaces aiding activation include:
- Antibodies for antigen binding.
- MHC molecules that present antigen peptides to T cells.
- CD40 receptors which receive signals from T cell CD40L.
- Complement receptors facilitating the immune response.

MHC Function

B cells endocytose antigens, process them, and present peptide fragments on MHC molecules for T cell recognition.

T Cell Interaction Requirement

T cells can only recognize antigens presented by B cells through their MHC molecules.

Role of T Cells

T cells activate B cells via MHC recognition, provide necessary signals for B cell activation, and secrete cytokines to further stimulate B cell function.

MHC Activation Post-Antigen Binding

MHC molecules on B cells express antigenic peptides only after binding with an antigen.

Initial B Cell Activation Step

The first step involves cross-linking of B cell receptors (BCRs) by antigens, leading to B cell activation.

Signal Transduction

Signals from antigen cross-linking are conveyed through an Ig-alpha and Ig-beta heterodimer, activating a cascade resulting in B cell proliferation and differentiation.

Intracellular Signaling Pathways

Major intracellular signaling pathways initiated in B cell activation include:
- NF-AT pathway.
- NF-KB pathway.
- AP-1 pathway.

NF-AT Pathway

Involves PIP2 conversion to IP3 leading to Ca2+ and calmodulin activation, with subsequent dephosphorylation of NF-AT and its migration to the nucleus for cytokine production.

NF-KB Pathway

Involves PIP2 to DAG and activation of PKC which phosphorylates IKB, releasing active NF-KB to enter the nucleus and promote cytokine production.

AP-1 Pathway

Activated by Ras and Rac G proteins, leading to AP-1 transcription factor activation which enters the nucleus to stimulate cytokine expression.

B Cell Coreceptor Components

Coreceptor includes:
- CD19
- CD21 (CR2)
- CD81 (TAPA-1)

Coreceptor Amplification

Coreceptor binds to bacteria/antigens and delivers a strong activation signal when complement fragments interact with CR2/CD21.

T Helper Cell Interaction

Activation of resting B cells by T helper cells relies on CD40-CD40L costimulatory interaction.

Negative Signaling Mechanism

B cell activation needs to be regulated; Fc receptors (CD32) can inhibit signaling by phosphorylating ITIMs to downregulate Ig synthesis and B cell effectiveness.

Antibody-Secreting B Cell Type

Plasma cells, or effector B cells, are responsible for antibody secretion.

CD19 Marker Specificity

CD19 is generally present on all B cells except for plasma cells.

Unique Feature of CD81

CD81 spans the transmembrane domain four times, denoting its distinctive structure among B cell coreceptor components.

T-Independent Antigens

TI-1 antigens activate B cells via BCRs and Toll-like receptors, highlighting the complexity of B cell activation stimuli.

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Explore the key concepts of B cell activation through this comprehensive flashcard quiz. Learn about the mechanisms of activation, including the roles of T cells and cytokines in this essential immune response. Ideal for students of immunology or anyone interested in the adaptive immune system.