Plasma Cell Disorders Flashcards
Describe the morphology, location, and function of normal plasma cells in the human body
Morphology
o 2-3x size of a small lymphocyte
o Round, eccentric (off to one side) nucleus
o Chromatin clumps = “clock face” appearance
o Pale perinuclear area from Golgi apparatus
o Deep blue cytoplasm
Location
o Lymph nodes, bone marrow, mucosa, spleen, other tissues with lymphoid cells
• Not normally found in blood
o B cells: express CXCR5 → directed to CXCL13-expressing germinal centers
o Plasma cells: CXCR5 expression decreases and CXCR4 expression increases → directed to CXCL12-expression marrow stromal cells
Function:
o Terminally differentiated B lymphocytes
Secrete antibodies in response to antigenic stimulation:
• Neutralization = Ab prevents bacterial adherence
• Opsonization = Ab promotes phagocytosis
• Complement activation = Ab activates complement, enhancing opsonization and lyses some bacteria
Describe the normal plasma cell biology
o Precursor B cell → VDJ recombination → naïve mature B cell (expresses surface Ig)
o Circulates in peripheral blood and primary follicles & mantle zone of lymph nodes
Antigen stimulation:
Some differentiate into short-lived IgM-producing plasma cells
Some proliferate as Follicle Center Cells (FCC) in germinal centers
• Interact with dendritic cells and T cells
• Stimulate B cells → class switching to IgG, IgA or IgE-producers
• Also undergo somatic hypermutation = increases affinity
• Some become memory and some become plasma cells
Most long-lived cells → migrate to bone marrow
• Plasma cell clone = group of plasma cells that secrete the same Ig molecule
Different stages of maturation have different antigens Plasma cells: • Cytoplasmic (but NOT surface Ig) • Lose typical B cell markers (CD20) • High expression of CD38 and CD138
Describe structure of immunoglobulins
Components: 5 types of heavy chain: • Gamma γ • Mu μ • Alpha α • Delta δ • Epsilon ε 2 types of light chains: • Kappa κ • Lambda λ Heavy chain gene: o V = variable o D = diversity o J = joingin o C = constant (determines Ig class)
Describe the differences among the various immunoglobulin classes.
IgG • Monomeric • Most abundant Ig in blood • Can cross the placenta and go into interstitial space • Can activate complement
IgM • Pentamer • Primarily intravascular space • Good complement activation • “Natural” antibodies (early response to antigen stimulus)
IgA
• Forms monomers and dimers
• Secreted into gut, lungs, milk, saliva, and tears
• Also present in blood, on epithelial surfaces, and on IgA-producing B cells
IgE
• Monomeric
• Associated with mast cells below epithelial surfaces
IgD
• Monomeric
• In blood at low levels
• Found on surface of mature, naïve B cells
Describe the following laboratory tests used to analyze immunoglobulins in serum and urine and explain the clinical utility of each test: Total protein
o Quantitative test for all proteins in blood (includes Ig’s)
Describe the following laboratory tests used to analyze immunoglobulins in serum and urine and explain the clinical utility of each test: Protein electrophoresis
Screening test for quantitative or qualitative abnormalities in serum or urine
• Especially good at detecting monoclonal immunoglobulin
Process: • Apply serum or urine to agarose gel • Electric current separates based on size and charge • Get a normal pattern: • Albumin = highest mobility • Alpha1 • Alpha2 • Beta • Gamma peak (mostly IgM & IgG, may have IgA)
Densitometric scanner generates tracings
• Able to estimate amount of protein from area under peak
• Report as percentage of total serum protein
Normally = polyclonal
If narrow peak in gamma region = presence of abnormally large clone of plasma cells
• “M protein/M component/M spike/paraprotein”
Other abnormal results:
• Hypogammaglobinemia
• Polyclonal gammopathy (characteristic of inflammatory response)
o Normal urine = minimal amount of albumin
• Can detect monoclonal light chains in urine in clonal plasma cell disorders
• “Bence Jones protein”
Result = need to look at BOTH serum and urine protein electrophoresis
Ex: in Multiple myeloma:
• Serum = large monoclonal band in gamma region; small amount of free light chain
• Urine = small amount of intact monoclonal Ig; large amount of monoclonal light chain and albumin
Ex: in Light chain myeloma:
• Serum shows decreased amount of intact Ig (reciprocal reduction in Ig’s = appears like hypoglobinemia)
• Urine shows large monoclonal free light chain
Describe the following laboratory tests used to analyze immunoglobulins in serum and urine and explain the clinical utility of each test: Immunofixation
o Identifies Ig class and type of light chain in monoclonal Ig
Process:
• Separate proteins via electrophoresis (same sample in each lane)
• Expose to antibody (ant-IgG, anti-IgA, anti-IgM, anti-kappa, or anti-lambda)
• Binds and immobilizes target Ig or light chain in gel
• Wash away unfixed protein
• Stain gel
