B Cell Activation Fundamentals

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.