Bone marrow - nonneoplastic
Normal
Lymphocyte maturation

Author: Dragos Luca, M.D. (see Authors page)

Revised: 3 July 2017, last major update August 2012

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Bone marrow [title] lymphocyte [title] maturation

Cite this page: Lymphocyte maturation. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/bonemarrowlymphocytematuration.html. Accessed November 21st, 2017.
Definition / general
  • Lymphocyte precursors originate in bone marrow
  • Mature lymphocytes are present in variable proportions in the bone marrow: children < 24 months of age may have up to 60%; adults usually have < 20% but some develop lymphoid aggregates (nonparatrabecular), especially with age
  • Unlike other hematopoietic cells, terminal differentiation of mature lymphocytes takes place in secondary lymphoid organs after they leave the bone marrow
  • Mature to B cells (humoral immune response) or T/NK cells (cell mediated immune response)
  • B cells complete most of their development within the bone marrow, but T cells are generated in the thymus from precursor cells that migrate from the bone marrow
  • Recombination assembly of Ig and TCR genes represents the main process in the development of B and T cells (regulated by RAG-1, RAG-2 and TdT)
  • Initially (children) have B:T cell ratio ~2:1; after 4 - 5 years of age, proportion of B cells decreases and T cells increases, reaching adult levels during adolescence (1:4 - 5)
B cell maturation
  • B cell development in marrow is dependent on CD10+ stromal cells (J Pathol 2005;205:311), which form specific, adhesive contacts with developing B lineage cells and also provide growth factors (stem cell factor, IL7, stromal cell derived factor 1)
  • Earliest stem cells are in subendosteum, adjacent to inner bone surface; with maturation, B lineage cells move towards central axis of marrow; final stages of development of immature B cells occur in peripheral lymphoid organs (spleen, lymph nodes)
  • Germline B cells undergo a series of Ig gene rearrangements to produce a heavy chain (μ) followed by light chains (κ or λ)
  • Commitment to B lineage was initially thought to be indicated by CD79; subsequent studies showed that cytoplasmic CD22 appears to be the most specific B cell marker
  • A minor subset of B cells also express CD5 (T cell marker)
  • Plasma cells are last stage of B cell maturation, express CD38 but lose CD19
T/NK cell maturation
  • T cells migrate from bone marrow to thymus and mature via TCR gene rearrangements
  • Most specific T cell marker appears to be cytoplasmic CD3
  • During thymic maturation sequence, T cells are initially double negative for CD4 and CD8 (pro and prethymocytes), then double positive (cortical thymocytes), then express either CD4 or CD8 (medullary thymocytes)
  • In NK cells, rearrangements of T cell receptor genes do not occur; proportion of NK cells in bone marrow does not change with age
  • Most NK cells (both true and cytotoxic) are morphologically large granular lymphocytes
Microscopic (histologic) description
  • Lymphocytes diffusely scattered throughout interstitium; represent 10 - 15% of marrow cells in adults; aggregates often present
  • Different subsets (B, T, NK) appear morphologically similar: small to large size, variable amount of cytoplasm, round nuclei, dense chromatin, variable inconspicuous nucleoli
Microscopic (histologic) images

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Normal lymphocytes

Movement of B lineage cells with maturation

Immunophenotype
  • Earliest immunologically recognizable B cells: TdT, CD34, CD79a, HLA-DR, +/-CD10 and +/-CD45; they subsequently acquire CD19, cCD22, CD22 and CD20
  • Pre B cells: +/-TdT, HLA-DR, CD19, CD10, CD20, CD22, CD79a, CD45 and cμ
  • Mature B cells: HLA-DR, CD19, CD20, CD22, CD79a, CD79b, CD45 and sIg

  • Precursor T cells: TdT, CD34, cCD3, CD2, CD5, CD7, CD38, +/-CD1a and +/-CD45; they are initially double negative for CD4 and CD8 (pro and prethymocytes), then double positive (cortical thymocytes) and then they only express either CD4 or CD8 (medullary thymocytes)
  • Mature T cells: CD2, CD3, CD5, CD7; CD45, either CD4 or CD8

  • NK cells: CD16, CD56, CD57, +/-sCD3, +/-CD8, +/-CD2, +/-CD7 and +/- cytotoxic proteins (perforin, granzyme, etc.)
Electron microscopy images

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Small lymphocyte

With cytoplasmic projections