Lecture Notes on B and T Cells and Lymphoma

Introduction to B and T Cells

• Overview of B and T cells and their role in the immune system.
• Key organs associated with B and T cells:
  • Bone Marrow
  • Thymus
  • Lymph Node

Development of T Cells

• Precursors in Bone Marrow:
  • Lymphoid progenitor cells can become either T or B cells.
• Thymus Development:
  • Precursor T cells enter thymus and become double negative thymocytes (negative for both CD4 and CD8).
  • Development into CD4 naive T cells (CD4 receptor) or CD8 naive T cells (CD8 receptor).
• Activation:
  • Naive T cells move to lymph nodes to become activated.

Development of B Cells

• Bone Marrow Development:
  • Precursor B cells undergo VDJ recombination with the enzyme RAG1/2.
  • Form naive B cells with surface-bound IgM antibodies.
• Activation in Lymph Nodes:
  • Naive B cell recognizes an antigen, phagocytizes it, presents on MHC class II.
  • Co-stimulation with CD4 T cells leads to B cell activation.
  • Cytokines from T cells trigger B cell proliferation into centroblasts.

Somatic Hypermutation and Selection

• During proliferation:
  • Centroblasts undergo somatic hypermutation, changing the variable region of antibodies, leading to varied affinities for antigens.
• Transition to Centrocytes:
  • Centrocytes sample antigens; those with decreased affinity undergo apoptosis, while those with increased affinity survive and proliferate.

B Cell Differentiation

• Activated B cells can differentiate into:
  • Memory B cells
  • Plasma cells (which secrete antibodies)
• Class switching occurs, allowing B cells to produce different antibody classes (IgE, IgA, IgG).

Overview of Lymphoma

• Definition: Tumors arising from T or B cell development.
• Types of Lymphoma:
  • Hodgkin's Lymphoma
  • Non-Hodgkin's Lymphoma (focus of the lecture)

Non-Hodgkin's Lymphoma

• Increasing prevalence, sixth most frequent cancer.
• Risk Factors:
  • Immunological (e.g., HIV, autoimmune diseases)
  • Viral (e.g., EBV, HCV)
  • Genetic (e.g., Klinefelter syndrome, SCID)
  • Environmental (e.g., pesticides, smoking)

Types of Non-Hodgkin's Lymphoma

T Cell Lymphomas:

• Arise during T cell development in the thymus or lymph nodes.
• Less common than B cell lymphomas.

B Cell Lymphomas:

• More prevalent due to genetic changes during development.
• Key subtypes include:
  • Mantle Cell Lymphoma
  • Burkitt's Lymphoma
  • Diffuse Large B-Cell Lymphoma (DLBCL)
    • Notable for 60% five-year survival rate.
  • Follicular Lymphoma
  • Chronic Lymphocytic Leukemia (CLL) / Small Lymphocytic Lymphoma (SLL)

Pathophysiology of Lymphomas

• Arise through genetic changes:
  • Translocations (e.g., Bcl-2, Bcl-6)
  • Mutations and Amplifications (e.g., p53, Bcl-2, Bcl-6, MYC)
• Somatic hypermutation and class switching can lead to mutations resulting in lymphoma.

Conclusion

• Summary of B and T cell development and the implications for understanding lymphomas.
• Emphasis on genetic factors leading to the development of lymphomas.