B Cell Maturation and development's regulation - IMMUNOLOGY

This presentation will give brief idea about the b cell maturation regulation using different transcription factors, cytokine and selection mechanism.

1. Regulation of B-Cell Development and Maturation Elia Naqvi 24-PBT-014

2. Introduction • B cells are crucial for adaptive immunity. • Development occurs in two phases: - Antigen-independent (Bone marrow) - Antigen-dependent (Peripheral organs) • Regulated by transcription factors, cytokines, and selection mechanisms.

3. Early B-Cell Development and Differentiation • HSCs → CLPs → B-cell progenitors. • Key signals: - CXCL12: Retains progenitors - SCF-c-Kit: Ensures survival - IL-7-IL7R: Promotes B-cell lineage commitment.

4. Bone Marrow Microenvironment and Stromal Cell Support • Stromal cells provide essential signals: - CXCL12 → Pre-pro B cell retention - IL-7 → Pro-B to Pre-B transition - SCF → Maintains progenitors • Adhesion molecules (VLA-4, VCAM-1) retain B-cell precursors.

5. Transcription Factor Regulation in B-Cell Lineage Commitment • EBF1 & E2A → Activate early B-cell genes. • PAX5 → Enforces B-cell fate, blocks alternative differentiation. • Sox4 & LEF1 → Support survival of early pro-B cells. • IRF4 & IRF8 → Aid differentiation. • Bcl-6 → Required for germinal center B cells. • Blimp-1 → Suppresses Bcl-6, promotes plasma cell fate.

6. Immunoglobulin Gene Rearrangement and Pre-BCR Checkpoint • Heavy Chain Rearrangement: - D to JH (early pro-B) - VH to DJH (late pro-B, requires PAX5) • Light Chain Rearrangement in small pre-B cells. • Pre-BCR Checkpoint: - Ensures productive heavy chain. - Failure → Apoptosis.

7. Immature B Cell Checkpoint and Negative Selection • Immature B cells express mIgM . • Self-reactive B cells undergo: - Clonal deletion (Apoptosis) - Receptor editing (RAG1/2 reactivation) - Anergy (Unresponsiveness) • Negative Selection ensures central tolerance.

8. Cytokine and Growth Factor Regulation in B-Cell Development • IL-7: Pro-B to Pre-B transition. • BLyS /BAFF: Essential for T2 to mature B-cell transition. • IL-4, IL-3: Promote B-cell differentiation. • L-BCGF: Supports late-stage maturation.

9. Transitional B-Cell Maturation in the Spleen • T1 B Cells: - Highly sensitive to negative selection. - Markers: mIgMhi , CD93+, CD24+. • T2 B Cells: - Express CD21, CD23, BAFF-R. - BAFF signaling promotes survival and maturation.

10. Mature B-Cell Subtypes & Functional Regulation • Follicular B Cells (B-2): - Circulate between blood and lymphoid organs. - Require T-cell help for activation. • Marginal Zone (MZ) B Cells: - Located in the spleen. - Respond to blood-borne antigens. • B-1 Cells: - Found in peritoneal and pleural cavities. - Produce T-independent antibodies.

11. Summary of Key Regulatory Mechanisms • Lineage Commitment: IL-7, CXCL12, SCF, c-Kit. • Transcription Factors: EBF1, PAX5, E2A, Sox4, IRF4, IRF8. • Checkpoints: Pre-BCR selection, Negative selection. • Self-Tolerance: Clonal deletion, Receptor editing, Anergy. • Cytokine Support: IL-7, BLyS /BAFF, IL-4, IL-3.

12. Conclusion • B-cell development is tightly regulated by transcription factors, cytokines, and receptor-mediated checkpoints. • Self-reactivity is eliminated through negative selection to ensure immune tolerance. • Mature B cells differentiate into diverse functional subsets with specialized immune roles.

13. Thank you.