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Lymphoma - B cell neoplasms

Lymph nodes

Normal lymphocyte development - B cells


Reviewer: Nikhil Sangle, M.D., University of Utah and ARUP Laboratories (see Reviewers page)
Revised: 7 February 2012, last major update January 2011
Copyright: (c) 2001-2010, PathologyOutlines.com, Inc.

General
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● Progressive maturation of hematopoietic stem cells through several stages to ultimately give rise to mature B cell pool that has been selected for reactivity against non-self antigens (Expert Rev Clin Immunol 2010;6:765)
● Develop from stem cells of yolk sac, fetal liver, spleen and bone marrow
● B cells complete most of their development within the bone marrow, in contrast to T cells that mature within the thymus
● In intersinusoidal bone marrow, hematopoeitic stem cells mature to early lymphoid progenitors, the pro-B, pre-B stages
● Developmental stages are in close contact with slender CD10+ stromal cells or their extensions, which allows tightly regulated signaling (J Pathol 2005;205:311)
● 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)

Physiology
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● B cells express surface immunoglobulin (Ig), composed of 2 heavy (H) and 2 light (L) chains (either kappa or lambda)
● B cell antigen receptor loci may have 4 types of modification (a) recombination of variable, diversity and joining regions (VDJ); (b) somatic hypermutation of V segments; (c) immunoglobulin heavy chain gene class switching; and (d) receptor editing
● Early B cell precursor is TdT+, CD34+, HLA-DR+, then undergoes heavy (H) chain rearrangement and adds CD19, then adds CD10, then adds IgM heavy chain; then adds light (L) chain rearrangement and adds cytoplasmic IgM with heavy and light chains, then B cells express IgM and IgD with the same binding site, then adds CD20 (now called preB cell); then adds surface Ig, then adds CD21 and CD22 and drops TdT (now called B cell)
● If B cell encounters an antigen that interacts with its variable region, it becomes a plasma cell
● Precursor B cells contain immunoglobulin related components but not immunoglobulin; express CD179a and CD179b (precursor to light chains) as part of their pre-B cell receptor, which disappears when replaced with conventional light chains
● B cells express surface immunoglobulin, consisting of 2 heavy chains and 2 light chains (kappa or lambda); immunoglobulin is associated with CD79a/CD79b complex to form a B cell antigen receptor complex
● IgH gene (heavy chain of immunoglobulin) is at 14q32; variable portion is coded by VDJ regions
● IgL gene (light chain of immunoglobulin): kappa is at 2p11, lambda is at 22q11; no diversity region is present
● Heavy chain isotype switch: determines if immunoglobulin is IgM, IgD, IgG1-4, IgA1-2 or IgE (9 constant regions); mediated by switch genes

Clinical features
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● B cell lymphomas: a clonal light chain rearrangement is usually specific for the presence of a B cell neoplasm
● X linked agammaglobulinemia: no B cell development
● Defects in receiving T cell signals can cause hyper IgM syndrome (J Allergy Clin Immunol 2010;125:778)

Diagrams
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B cell biomarker expression during development

B cell development

Microenvironmental niches in the bone marrow required for B-cell development

B cell response to antigen

Micro images
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Germinal center

Positive stains
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● Varies by developmental state, but typically CD19, CD20, CD79a

Negative stains
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● CD2, CD3, CD4, CD8

Additional references
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Wikipedia

End of Lymphoma - B cell neoplasms > Lymph nodes > Normal lymphocyte development - B cells


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