Maturation and Selection of B and T cells

B Cell Maturation

• e-B cells express a functional μ heavy chain, an essential component of the pre-BCR and BCR.
• Pre-B cells that cannot express a pre-BCR or receive pre-BCR signals die by programmed cell death (apoptosis).
• The IgM-expressing B lymphocyte is the immature B cell.
• The final maturation step involves coexpression of IgD with IgM through alternatively spliced H chain transcripts.
• Coexpression of IgM and IgD enables B cells to respond to antigens in peripheral lymphoid tissues.
• This coexpression occurs either in the bone marrow or after B cells leave the bone marrow and go to the spleen.

Selection of Mature B Cells

• Positive selection is based on the expression of complete antigen receptors, not on the recognition specificity of these cells.
• Negative selection: immature B cells that bind self-antigens in the bone marrow may reexpress the VDJ recombinase enzyme and undergo additional light-chain V-J recombination to change their receptor specificity (receptor editing).
• If B cells are still self-reactive after receptor editing, they may die by apoptosis (deletion).

Maturation and Selection of T Lymphocytes

• T cell progenitors migrate from the bone marrow to the thymus for maturation.
• Pro-T cells (double-negative thymocytes) do not express CD4 or CD8; IL-7 produced in the thymus stimulate their proliferation.
• CD4 and CD8 are co-receptors that display strong specificity for MHC class II and I, respectively.

Maturation of T Lymphocytes

• Successful V(D)J recombination leads to the expression of TCR β-chain protein on the cell surface with pre-Tα protein, forming the pre-TCR complex of pre-T cells.
• The pre-TCR complex delivers intracellular signals that promote survival, proliferation, and TCR α gene recombination.
• Surviving cells express the complete αβ TCR and both CD4 and CD8 coreceptors (double-positive T cells or double-positive thymocytes).

Positive Selection of T Cells

• MHC I and MHC II molecules are recognized by CD8+ and CD4+ T cells, respectively, in the thymus.
• Positive selection of T cells involves recognition of MHCII-self peptide complexes by CD4+ T cells and MHCI-self peptide complexes by CD8+ T cells.

Negative Selection of T Cells

• T cells that strongly interact with class I or II MHC-peptide complexes in the thymus undergo apoptosis.
• Negative selection removes autoreactive T cells that recognize self-MHC-self peptide complexes with high affinity.

Summary

• Lymphocytes undergo multiple selection steps during maturation to preserve useful specificities based on the expression of intact antigen receptor components and what they recognize (self or nonself).
• Both positive and negative selection are mediated by recognition of the same set of self MHC-self peptide complexes in the thymus.