The immunoglobulinopathies: from physiopathology to diagnosis.
The diversity of immunoglobulins (Igs) results mainly from recombinations of numerous genes within the heavy (V(Heavy), D, and J(Heavy)) and within the light (V(Light), J(Light)) chain gene loci, and from somatic hypermutations occurring during the immune response of B-cells. Igs production is controlled by complex cellular and humoral mechanisms. Plasma of healthy individuals contains polyclonal Igs. Clonal expansion of cells producing antigen-specific Igs may result from physiological as well as from pathological immune events. Exquisitely sensitive and specific molecular biology techniques have been used to evaluate the clonal diversity of cells producing antigen-specific Ig. However, the application of such techniques is hampered by the necessity to collect the totality of antigen-specific B-cells for subsequent analysis, which is impossible to perform routinely in humans. In addition, these techniques do not provide quantitative information about the concentration of the circulating Igs. It is therefore necessary to use tools allowing study of the quantity of the circulating Igs, and more particularly to detect overproduction of a single homogeneous Ig resulting from the expansion of a B-cell clone secreting Igs. Here, we review the mechanisms of B-cell differentiation and Ig synthesis, discuss the diseases associated with clonal Ig production and review the methods available in the clinical laboratory for Ig analysis.
Service régional vaudois de transfusion sanguine, Lausanne, Switzerland. jean-daniel.tissot@chuv.hospvd.ch
Jean-Daniel
JD
Tissot
Dinh-Hao
DH
Vu
Vincent
V
Aubert
Philippe
P
Schneider
Françoise
F
Vuadens
David
D
Crettaz
Michel A
MA
Duchosal
D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000502:physiology; D001796:Blood Protein Disorders / Q000175:diagnosis / Q000503:physiopathology; D002454:Cell Differentiation / Q000502:physiology; D004586:Electrophoresis / Q000379:methods; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008970:Molecular Weight; D010265:Paraproteinemias / Q000175:diagnosis / Q000503:physiopathology; D020543:Proteome
D000911:Antibodies, Monoclonal; D007136:Immunoglobulins; D020543:Proteome