• T cells home to the perifollicular zones of the cortical areas of lymph nodes (paracortical areas) and to the periarteriolar sheaths surrounding the central arterioles of the spleen.
• B cells selectively accumulate in follicles of the lymph nodes and spleen.

T-Cell

• Early T-cell differentiation occurs in the thymus. The most immature T-cell precursors are negative for both CD4 and CD8. Thymocytes can become committed to either the γ-δ or α-β lineage.
  • As thymocytes within the α-β lineage mature, they gain expression of both CD4 and CD8. Normal thymocytes downregulate the expression of CD4 or CD8 before moving into the periphery as naïve T cells, which are subdivided into helper (CD4 +) and suppressor/cytotoxic (CD8 +) subsets.

• Early medullary thymocytes express both CD4 and CD8, but they then lose one or other of these structures.
• T cells develop from cells that have migrated to the thymus where they differentiate into mature T cells during passage from the cortex to the medulla.
• During this process, self‐reactive T cells are deleted (negative selection) whereas T cells with some specificity for host human leucocyte antigen (HLA) molecules are selected (positive selection).
• The cells also express one of two T‐cell antigen receptor heterodimers, αβ (>90%) or γδ (<10%).
  • The α, β, γ and δ genes of the TCRs each include V, D, J and C regions. During T‐cell ontogeny, rearrangements of these gene segments occur in a similar fashion to those for immunoglobulin genes, thus creating T cells expressing a wide variety (108 or more) of TCR structures
  • The T‐cell receptor consists of a number of components that together constitute the CD3 complex. Two antigen‐binding chains (α, β) are associated with several proteins (γ, δ, ε, ζ) that mediate signal transduction.
• T cells are unable to bind antigen free in solution and require it to be presented on APCs in the form of peptides held on the surface of HLA molecules. T cells recognize the antigen only when it is presented with ‘self’ HLA molecules and so are known as HLA‐restricted.
  • CD8+ T cells interact with peptide on a class I HLA molecule and the CD8 heterodimer interacts with the α3 domain of the class I protein.
  • The CD4 molecule on helper cells recognizes class II (HLA‐DP, ‐DQ and -DR) molecules, whereas the CD8 molecule recognizes class I (HLA‐A, ‐B and ‐C) molecules.

B-Cell

• B cells mature in the bone marrow and circulate in the peripheral blood until they undergo recognition of antigen.
• The first stage of B-cell development takes place in the bone marrow. Normal development of lymphopoiesis depends on the IKAROS family of transcription factors, which form multimeric complexes with other members, AIOLOS and HELIOS. These complexes are known as chromatin remodeling machines, and their targets induce a second wave of transcription factors, such as, PU.1, E2A, EBF, and PAX5, which, in turn, induce expression of the adaptor protein BLNK (SLP-65), CD19, VPREB, and λ5 (ie, markers specific of the B-cell lineage). BLNK regulates the transition from pro-B cells to preB cells, and PAX5 is necessary for V(D)J recombination. This early stage of development is independent of antigen and is followed by an antigen-dependent developmental stage in the peripheral lymphoid organs.