Updated: 8/7/2017

Lymphocyte Development and Structure

Review Topic
  • Lymphocyte development is complex and has several features including
    • localization to primary lymphoid organs such as
      • the bone marrow for B-cell development
      • the thymus for T-cell development
    • VDJ recombination in order to
      • rearrange genetic material
      • generate a unique B- or T-cell receptor
    • positive selection in order to
      • ensure all cells have functional receptors
    • proliferation in order to
      • expand the pool of potential lymphocytes
      • allow for broad protection against different types of antigens
    • negative selection in order to
      • remove cells that target self-antigens
      • protect against autoimmunity
  • There are many mechanisms to increase diversity during lymphocyte development such as
    • random recombination of genetic material during
      • VDJ recombination
    • random nucleotide addition to hypervariable regions by
      • the protein TdT
    • random assortment of different chains in receptor assembly
      • heavy chains with light chains in B-cells
      • alpha chains with beta chains in T-cells
    • somatic hypermuation after antigen exposure
      • only occurs in B-cells
B-Cell Development
  • B-cells develop in the bone marrow
    • develop a unique B-cell receptor
    • are tested to ensure that the receptor is functional
    • are further tested for self-reactivity to prevent autoimmunity
  • This development cycle is coordinated by the orderly progression through stages where
    • supporting cells give feedback at every stage
    • interaction strength of the B-cell receptor is monitored
Stages of B-Cell Development
Cell Type
Developmental Steps
Surface Receptor
Lymphoid stem cell
  • Commitment to B-cell lineage
  • None
  • Pleuripotent
Pro B-cell
  • Heavy chain VDJ recombination
  • Additional diversity from TdT modification
  • Heavy chain only
  • Recombination mediated by RAG proteins
  • Defect in RAG leads to Omenn syndrome with no mature B cells
Pre B-cell
  • Allelic exclusion to ensure only one heavy chain expressed
  • Positive selection
  • Proliferation
  • Pre B-cell receptor
  • Key step in monitoring activity of the recombined heavy chain
Immature B-cell
  • Light chain VJ recombination
  • Negative selection
  • IgM receptor
  • Inactivation of recombination machinery
  • Key step in tolerance
Mature B-cell
  • Exit into blood stream
  • IgM receptor
  • IgD receptor
  • Circulates and awaits activation by antigen
T-Cell Development  

  • T-cells migrate from the bone marrow to the thymus where they
    • develop a unique T-cell receptor
    • are tested to ensure that the receptor is functional
    • are further tested for self-reactivity to prevent autoimmunity
  • This development cycle is coordinated by the orderly progression through stages where
    • supporting cells give feedback at every stage
    • receptors that bind too strongly lead to developing T-cell death
    • the T-cell receptor undergoes selection in distinct compartments
Stages of T-Cell Development
Cell Type
Developmental Steps
Surface Proteins
T-cell precursor
  • Commitment to T-cell lineage
  • Migration to thymus
  • None
  • Lack of thymic development in DiGeorge syndrome
Double negative
  • Rearrangement of the β T-cell receptor chain
  • Proliferation
  • Pre T-cell receptor
  • Occurs in the thymic cortex
Double positive
  • Rearrangement of the α T-cell receptor chain
  • Expression of both CD4 and CD8
  • Positive selection against both class I and class II MHC
  • CD4
  • CD8
  • T-cell receptor
  • Key step in determining type of T-cell that develops
  • MHC II binding leads to CD4+ cells
  • MHC I binding leds to CD8+ cells
Single positive
  • Migration to medulla of thymus
  • Negative selection against self antigens
  • T-cell receptor
  • Either CD4 or CD8
  • The transcription factor AIRE allows medullary cells to express proteins from all areas of body
  • This ensure tolerance to vast majority of self antigens
Mature T-cell
  • Exit into blood stream
  • Awaits peripheral activation
  • T-cell receptor
  • Either CD4 or CD8
  • Circulates and awaits activation by antigen

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Questions (2)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2

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(M1.IM.74) A thymic sample from a fetus is examined. One cell type found was double-positive for the CD4 and CD8 receptors. What is the identity of these double-positive cells? Review Topic

QID: 100495

T-cell progenitors cells in the bone marrow








Immature T-cells of the thymic cortex




Immature T-cells of the thymic medulla








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