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Antibodies and Immunoglobulins: Title and subTitle BreakII. Normal Development and Changes in Disease FREE

John L. Fahey, MD
[+] Author Affiliations

Part I of this communication appeared in the Oct 4 issue. Reprint requests to National Cancer Institute, Bethesda, Md 20014.


From the Immunology Branch, National Cancer Institute, Bethesda, Md.


JAMA. 1965;194(3):255-258. doi:10.1001/jama.1965.03090160033009
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Antibody Response.—  Several days elapse following primary antigen administration before antibody is detected in the serum. In this interval, antigen recognition and immune cell sensitization are followed by development of antibody synthetic capacity and proliferation of antibody producing cells. A considerable amount of antibody synthesis must occur before circulating antibody becomes detectable. At least 1016 molecules of antibody have to be synthesized and be retained intravascularly in an 132 lb (60 kg) man to be detectable as 0.001 mg antibody per milliliter of serum.Antibody activity may be present in one or more components of the serum immunoglobulin system. Four classes of immunoglobulins have been identified: IgG (γG, 7S γ2-globulin), IgA (γA, β2A-globulin), IgM (γM, 18S γ1-macroglobulin) and IgD (yD). The distribution of these proteins, as detected by immunoelectrophoresis, is shown in Fig 1. The principal properties of the four major immunoglobulin classes were reviewed in a companion report.

REFERENCES

Fahey, J.L.:  Antibodies and Immunoglobulins: I. Structure and Function , JAMA , 194:71-74 ( (Oct 4) ) 1965;.
Smith, R.T., and Eitzman, D.V.:  Development of Immune Response. Characterization of Response of Human Infant and Adult to Immunization With Salmonella Vaccines , Pediatrics 33:163-183, 1964;.
Fink, C.W., et al:  Formation of Macroglobulin Antibodies: II. Studies on Neonatal Infants and Older Children , J Clin Invest 41:1422-1428, 1962;.
Uhr, J.W., et al:  Antibody Response to Bacteriophage Ø × 174 in Newborn Premature Infants , J Clin Invest 41:1509-1513, 1962;.
LoSpalluto, J., et al:  Formation of Macroglobulin Antibodies: I. Studies on Adult Humans , J Clin Invest 41:1415-1421, 1962;.
Bauer, D.C.: Mathies, M.J.; and Stavitsky, A.B.:  Sequences of Synthesis of γ1-Macroglobulin and γ2-Globulin Antibodies During Primary and Secondary Responses to Proteins, Salmonella Antigens and Phage , J Exp Med 117:889-907, 1963;.
Uhr, J.W., and Finkelstein, M.S.:  Antibody Formation: IV. Formation of Rapidly and Slowly Sedimenting Antibodies and Immunological Memory to Bacteriophage Ø × 174 , J Exp Med 117:457-477, 1963;.
Cohen, S., and Freeman, T.:  Metabolic Heterogeneity of Human γ-Globulins , Biochem J 76:475-487, 1960;.
Solomon, A.; Waldmann, T.A.; and Fahey, J.L.:  Metabolism of Normal 6.6S Gamma-Globulin in Normal Subjects and in Patients With Macroglobulinemia and Multiple Myeloma , J Lab Clin Med 62:1-17, 1963;.
Barth, W.F., et al : Metabolism of Human Gamma Macroglobulin , J Clin Invest 43:1036-1048, 1964;.
Sahiar, K., and Schwartz, R.S.:  Inhibition of 19S Antibody Synthesis by 7S Antibody , Science 145:395-397, 1964;.
Finkelstein, M.S., and Uhr, J.W.:  Specific Inhibition of Antibody Formation by Passively Administered 19S and 7S Antibody , Science 146:67-69, 1964;.
Silverstein A.M.:  Congenital Syphilis and Timing of Immunogenesis in Human Foetus , Nature 194:196, 1962;.
Brambell, F.W.R.:  Passive Immunity of Young Mammal , Biol Rev 33:488-527, 1958;.
Hitzig, W.H.:  Die Physiologische Entwicklung der Immunoglobuline (gamma und beta2-globuline) , Helv Paediat Acta 12:596-605, 1956;.
West, C.D., et al:  Immunoglobulin Levels From Newborn Period to Adulthood and in Immunoglobulin Deficiency States , J Clin Invest 41:2054-2064, 1962;.
Sell, S., and Fahey, J.L.:  Relationship Between γ-Globulin Metabolism and Low Serum γ-Globulin in Germfree Mice , J Immun 93:81-87, 1964;.
Dixon, F.J., et al:  Half-Life of Homologous Gamma Globulin (Antibody) in Several Species, J Exp Med 96:313-318, 1952;.
Solomon, A.:  Metabolism of Group I and Group II 7S γ-Globulin , Clin Res 12:238, 1964;.
Fahey, J.L., and Robinson, A.G.:  Factors Controlling Serum γ-Globulin Concentration , J Exp Med 118:845-868, 1963;.
Brambell, F.W.R.; Hemmings, W.A.; and Morris, I.G.:  Theoretical Model of γ-Globulin Catabolism , Nature 203:1352-1355, 1964;.
Solomon, A., and Tomasi, T.B., Jr.:  Metabolism of IgA (β2A) Globulin , Clin Res 12:452, 1964;.
Hitzig, W.H., and Willi, H.:  Hereditare Lympho-Phasmocytare Dysgenesie ("alymphocytose mit agammaglobulinamie") , Schweiz Med Wschr 91:1625-1633, 1961;.
Rosen, F.S.; Gitlin, D.; and Janeway, C.A.:  Alymphocytosis, Agammaglobulinemia, Homograft and Delayed Hypersensitivity: Study of Case , Lancet 2:380-381, 1962;.
Gitlin, D; Vawter, G.; and Craig, J.M.:  Thymic Alymphoplasia and Congenital Aleukocytosis , Pediatrics 33:184-192, 1964;.
Gitlin, D., et al: " Agammaglobulinemia ," in Lawrence, S. (ed.): Cellular and Humoral Aspects of Hypersensitivity States , New York: Paul B. Hoeber, Inc., 1959;, p 375.
Good, R.A., et al:  Clinical Investigation of Patients With Agammaglobulinemia and Hypogammaglobulinemia , Pediat Clin N Amer 7:397-433, 1960;.
Israel-Asselain, R.; Burtin, P.; and Chebat, J.:  Un Trouble Biologigue Nouveau: 1' agammaglobulinemie avec β2-macroglobulinemia , Bull Mem Soc Hop Paris 76:519, 1960;.
Hong, R., et al:  Antibody Deficiency Syndrome Associated With Beta2-Macroglobulinemia , J Pediat 61:831-842, 1962;.
Huntley, C.C.; Lafferty, J.W.; and Lyerly, A:  Antibody Deficiency Syndrome With Increased γ1M (β2M)-Globulins and Absent γ1A (β2A)-Globulins and γ2 (G)-Globulins , Pediatrics 32:407-415, 1963;.
Hinz, C.F., Jr., and Boyer, J.T.:  Dysgammaglobulinemia in Adult Manifested as Autoimmune Hemolytic Anemia: Serologic and Immunochemical Characterization of Antibody of Unusual Specificity , New Eng J Med 269:1329-1335, 1963;.
Rosen, F.S., and Bongas, J.A.:  Acquired Dysgammaglobulinemia: Elevation of 19S Gamma and Deficiency of 7S Gamma Globulin in Woman With Chronic Progressive Bronchiectasis , New Eng J Med 269:1336-1340, 1963;.
Fudenberg, H.H.; Heremans, J.F.; and Franklin, E.C.:  Hypothesis for Genetic Control of Synthesis of Gamma Globulins , Ann Inst Pasteur 104:155-168, 1963;.
Burtin, P.; Buffe, D; and Grabar, P.:  Les Hypogamma-Globulinemies Atypiques , Ann Inst Pasteur 106:519-542, 1964;.
Barth, W.F., et al:  Antibody Deficiency Syndrome: Selective Immunoglobulin Deficiency With Reduced Synthesis of γ and a Immunoglobulin Polypeptide Chains , Amer J Med , to be published.
Giedion, A., and Scheidegger, J.J.:  Kongenitale Immunparese Bei Fehlen Sperzifischer β2-Globuline und Quantitative Normalen γ-Globulinen , Helvet Paediat Acta 12:241-259, 1957;.
Barandun, S.; Cottier, H.; and Hassig, A.: " New Aspects of Agammaglobulinemia and Antibody Deficiency Syndrome ," in Immunopathology, 1st International Symposium , Basel, Switzerland, Benno Schwabe and Co., 1958;, p 60.
Gilbert, C., and Hong, R:  Qualitative and Quantitative Immunoglobulin Deficiency , Amer J Med 37:602, 1964;.
Levin, W.C., et al:  Selective A-Beta-2A-Globulinemia , Clin Res 11:294, 1963;.
Rockey, J.H., et al:  Beta-2A-Aglobulinemia in Two Healthy Men , J Lab Clin Med 63:205-212, 1964;.
Young, R.R.; Austen, K.F.; and Moser, H.W.:  Abnormalities of Serum γ1A-Globulin and Ataxia Telangiectasia , Medicine 43:423-433, 1964;.
Peterson, R.D.A.; Kelly, W.D.; and Good, R.A.:  Ataxia-Telangiectasia: Its Association With Defective Thymus, Immunological Deficiency, Disease and Malignancy , Lancet 1:1189-1193, 1964;.
Fireman, P.; Boesman, M.; and Gitlin, D.:  Ataxia Telangiectasia: Dysgammaglobulinemia With Deficient γ1A (β2A)-Globulin , Lancet 1:1193-1195, 1964;.
Heremans, J.F., et al:  Studies on "Abnormal" Serum Globulins (M-Components) in Myeloma, Macroglobulinemia and Related Diseases , Acta Med Scand 170 ( (suppl 367) ): 1-126, 1961;.
Bernier, G.M., and Putnam, F.W.:  Myeloma Proteins and Macroglobulins: Hallmarks of Disease and Models of Antibodies , Progr Hemat 4:160-186, 1964;.
Mannik, M., and Kunkel, H.G.:  Classification of Myeloma Proteins, Bence Jones Proteins and Macroglobulins Into Two Groups on Basis of Common Antigenic Characters , J Exp Med 116:859-877, 1962;.
Fahey, J.L., and Soloman, A.:  Two Types of γ-Myeloma Proteins, β2A-Myeloma Proteins, γ1-Macroglobulins and Bence Jones Proteins Identified by Two Groups of Common Antigenic Determinants , J Clin Invest 42:811-822, 1963;.
Edelman, G.M., and Gaily, J.A.:  Nature of Bence Jones Proteins. Chemical Similarities to Polypeptide Chains of Myeloma Globulins and Normal γ-Globulins , J Exp Med 116:207-227, 1962;.
Franklin, E.C., et al:  Heavy Chain Disease—New Disorder of Serum γ-Globulins , Amer J Med 37:332-350, 1964;.
Osserman, E., and Takatsuki, K.:  Clinical and Immunochemical Studies of Four Cases of H γ2-Chain Disease , Amer J Med 37:357-384, 1964;.
Heremans, J.F.: Les Globulines Seriques de Systeme Gamma , Brussels: Arscia, 1960;.
Grabar, P., and Burtin, P.: Analyse Immunoelectrophoretique , Paris: Masson & Cie, 1960;,149-226.
Holman, H.; Nickel, W.F., Jr.; and Sleisenger, M.H.:  Hypoproteinemia Antedating Intestinal Lesions, and Possibly Due to Excessive Serum Protein Loss Into Intestine , Amer J Med 27:963-975, 1959;.
Blainey, J.D., et al:  Nephrotic Syndrome: Diagnosis by Renal Biopsy and Biochemical and Immunologic Analyses Related to Response to Steroid Therapy , Quart J Med 29:235-256, 1960;.
Mattern, P., et al  Immunochemical Study of β2-Macroglobulin in Sera of Patients With African T. Gambiense Trypanosomiasis , Ann Inst Pasteur 101:382-388, 1961;.

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Fahey, J.L.:  Antibodies and Immunoglobulins: I. Structure and Function , JAMA , 194:71-74 ( (Oct 4) ) 1965;.
Smith, R.T., and Eitzman, D.V.:  Development of Immune Response. Characterization of Response of Human Infant and Adult to Immunization With Salmonella Vaccines , Pediatrics 33:163-183, 1964;.
Fink, C.W., et al:  Formation of Macroglobulin Antibodies: II. Studies on Neonatal Infants and Older Children , J Clin Invest 41:1422-1428, 1962;.
Uhr, J.W., et al:  Antibody Response to Bacteriophage Ø × 174 in Newborn Premature Infants , J Clin Invest 41:1509-1513, 1962;.
LoSpalluto, J., et al:  Formation of Macroglobulin Antibodies: I. Studies on Adult Humans , J Clin Invest 41:1415-1421, 1962;.
Bauer, D.C.: Mathies, M.J.; and Stavitsky, A.B.:  Sequences of Synthesis of γ1-Macroglobulin and γ2-Globulin Antibodies During Primary and Secondary Responses to Proteins, Salmonella Antigens and Phage , J Exp Med 117:889-907, 1963;.
Uhr, J.W., and Finkelstein, M.S.:  Antibody Formation: IV. Formation of Rapidly and Slowly Sedimenting Antibodies and Immunological Memory to Bacteriophage Ø × 174 , J Exp Med 117:457-477, 1963;.
Cohen, S., and Freeman, T.:  Metabolic Heterogeneity of Human γ-Globulins , Biochem J 76:475-487, 1960;.
Solomon, A.; Waldmann, T.A.; and Fahey, J.L.:  Metabolism of Normal 6.6S Gamma-Globulin in Normal Subjects and in Patients With Macroglobulinemia and Multiple Myeloma , J Lab Clin Med 62:1-17, 1963;.
Barth, W.F., et al : Metabolism of Human Gamma Macroglobulin , J Clin Invest 43:1036-1048, 1964;.
Sahiar, K., and Schwartz, R.S.:  Inhibition of 19S Antibody Synthesis by 7S Antibody , Science 145:395-397, 1964;.
Finkelstein, M.S., and Uhr, J.W.:  Specific Inhibition of Antibody Formation by Passively Administered 19S and 7S Antibody , Science 146:67-69, 1964;.
Silverstein A.M.:  Congenital Syphilis and Timing of Immunogenesis in Human Foetus , Nature 194:196, 1962;.
Brambell, F.W.R.:  Passive Immunity of Young Mammal , Biol Rev 33:488-527, 1958;.
Hitzig, W.H.:  Die Physiologische Entwicklung der Immunoglobuline (gamma und beta2-globuline) , Helv Paediat Acta 12:596-605, 1956;.
West, C.D., et al:  Immunoglobulin Levels From Newborn Period to Adulthood and in Immunoglobulin Deficiency States , J Clin Invest 41:2054-2064, 1962;.
Sell, S., and Fahey, J.L.:  Relationship Between γ-Globulin Metabolism and Low Serum γ-Globulin in Germfree Mice , J Immun 93:81-87, 1964;.
Dixon, F.J., et al:  Half-Life of Homologous Gamma Globulin (Antibody) in Several Species, J Exp Med 96:313-318, 1952;.
Solomon, A.:  Metabolism of Group I and Group II 7S γ-Globulin , Clin Res 12:238, 1964;.
Fahey, J.L., and Robinson, A.G.:  Factors Controlling Serum γ-Globulin Concentration , J Exp Med 118:845-868, 1963;.
Brambell, F.W.R.; Hemmings, W.A.; and Morris, I.G.:  Theoretical Model of γ-Globulin Catabolism , Nature 203:1352-1355, 1964;.
Solomon, A., and Tomasi, T.B., Jr.:  Metabolism of IgA (β2A) Globulin , Clin Res 12:452, 1964;.
Hitzig, W.H., and Willi, H.:  Hereditare Lympho-Phasmocytare Dysgenesie ("alymphocytose mit agammaglobulinamie") , Schweiz Med Wschr 91:1625-1633, 1961;.
Rosen, F.S.; Gitlin, D.; and Janeway, C.A.:  Alymphocytosis, Agammaglobulinemia, Homograft and Delayed Hypersensitivity: Study of Case , Lancet 2:380-381, 1962;.
Gitlin, D; Vawter, G.; and Craig, J.M.:  Thymic Alymphoplasia and Congenital Aleukocytosis , Pediatrics 33:184-192, 1964;.
Gitlin, D., et al: " Agammaglobulinemia ," in Lawrence, S. (ed.): Cellular and Humoral Aspects of Hypersensitivity States , New York: Paul B. Hoeber, Inc., 1959;, p 375.
Good, R.A., et al:  Clinical Investigation of Patients With Agammaglobulinemia and Hypogammaglobulinemia , Pediat Clin N Amer 7:397-433, 1960;.
Israel-Asselain, R.; Burtin, P.; and Chebat, J.:  Un Trouble Biologigue Nouveau: 1' agammaglobulinemie avec β2-macroglobulinemia , Bull Mem Soc Hop Paris 76:519, 1960;.
Hong, R., et al:  Antibody Deficiency Syndrome Associated With Beta2-Macroglobulinemia , J Pediat 61:831-842, 1962;.
Huntley, C.C.; Lafferty, J.W.; and Lyerly, A:  Antibody Deficiency Syndrome With Increased γ1M (β2M)-Globulins and Absent γ1A (β2A)-Globulins and γ2 (G)-Globulins , Pediatrics 32:407-415, 1963;.
Hinz, C.F., Jr., and Boyer, J.T.:  Dysgammaglobulinemia in Adult Manifested as Autoimmune Hemolytic Anemia: Serologic and Immunochemical Characterization of Antibody of Unusual Specificity , New Eng J Med 269:1329-1335, 1963;.
Rosen, F.S., and Bongas, J.A.:  Acquired Dysgammaglobulinemia: Elevation of 19S Gamma and Deficiency of 7S Gamma Globulin in Woman With Chronic Progressive Bronchiectasis , New Eng J Med 269:1336-1340, 1963;.
Fudenberg, H.H.; Heremans, J.F.; and Franklin, E.C.:  Hypothesis for Genetic Control of Synthesis of Gamma Globulins , Ann Inst Pasteur 104:155-168, 1963;.
Burtin, P.; Buffe, D; and Grabar, P.:  Les Hypogamma-Globulinemies Atypiques , Ann Inst Pasteur 106:519-542, 1964;.
Barth, W.F., et al:  Antibody Deficiency Syndrome: Selective Immunoglobulin Deficiency With Reduced Synthesis of γ and a Immunoglobulin Polypeptide Chains , Amer J Med , to be published.
Giedion, A., and Scheidegger, J.J.:  Kongenitale Immunparese Bei Fehlen Sperzifischer β2-Globuline und Quantitative Normalen γ-Globulinen , Helvet Paediat Acta 12:241-259, 1957;.
Barandun, S.; Cottier, H.; and Hassig, A.: " New Aspects of Agammaglobulinemia and Antibody Deficiency Syndrome ," in Immunopathology, 1st International Symposium , Basel, Switzerland, Benno Schwabe and Co., 1958;, p 60.
Gilbert, C., and Hong, R:  Qualitative and Quantitative Immunoglobulin Deficiency , Amer J Med 37:602, 1964;.
Levin, W.C., et al:  Selective A-Beta-2A-Globulinemia , Clin Res 11:294, 1963;.
Rockey, J.H., et al:  Beta-2A-Aglobulinemia in Two Healthy Men , J Lab Clin Med 63:205-212, 1964;.
Young, R.R.; Austen, K.F.; and Moser, H.W.:  Abnormalities of Serum γ1A-Globulin and Ataxia Telangiectasia , Medicine 43:423-433, 1964;.
Peterson, R.D.A.; Kelly, W.D.; and Good, R.A.:  Ataxia-Telangiectasia: Its Association With Defective Thymus, Immunological Deficiency, Disease and Malignancy , Lancet 1:1189-1193, 1964;.
Fireman, P.; Boesman, M.; and Gitlin, D.:  Ataxia Telangiectasia: Dysgammaglobulinemia With Deficient γ1A (β2A)-Globulin , Lancet 1:1193-1195, 1964;.
Heremans, J.F., et al:  Studies on "Abnormal" Serum Globulins (M-Components) in Myeloma, Macroglobulinemia and Related Diseases , Acta Med Scand 170 ( (suppl 367) ): 1-126, 1961;.
Bernier, G.M., and Putnam, F.W.:  Myeloma Proteins and Macroglobulins: Hallmarks of Disease and Models of Antibodies , Progr Hemat 4:160-186, 1964;.
Mannik, M., and Kunkel, H.G.:  Classification of Myeloma Proteins, Bence Jones Proteins and Macroglobulins Into Two Groups on Basis of Common Antigenic Characters , J Exp Med 116:859-877, 1962;.
Fahey, J.L., and Soloman, A.:  Two Types of γ-Myeloma Proteins, β2A-Myeloma Proteins, γ1-Macroglobulins and Bence Jones Proteins Identified by Two Groups of Common Antigenic Determinants , J Clin Invest 42:811-822, 1963;.
Edelman, G.M., and Gaily, J.A.:  Nature of Bence Jones Proteins. Chemical Similarities to Polypeptide Chains of Myeloma Globulins and Normal γ-Globulins , J Exp Med 116:207-227, 1962;.
Franklin, E.C., et al:  Heavy Chain Disease—New Disorder of Serum γ-Globulins , Amer J Med 37:332-350, 1964;.
Osserman, E., and Takatsuki, K.:  Clinical and Immunochemical Studies of Four Cases of H γ2-Chain Disease , Amer J Med 37:357-384, 1964;.
Heremans, J.F.: Les Globulines Seriques de Systeme Gamma , Brussels: Arscia, 1960;.
Grabar, P., and Burtin, P.: Analyse Immunoelectrophoretique , Paris: Masson & Cie, 1960;,149-226.
Holman, H.; Nickel, W.F., Jr.; and Sleisenger, M.H.:  Hypoproteinemia Antedating Intestinal Lesions, and Possibly Due to Excessive Serum Protein Loss Into Intestine , Amer J Med 27:963-975, 1959;.
Blainey, J.D., et al:  Nephrotic Syndrome: Diagnosis by Renal Biopsy and Biochemical and Immunologic Analyses Related to Response to Steroid Therapy , Quart J Med 29:235-256, 1960;.
Mattern, P., et al  Immunochemical Study of β2-Macroglobulin in Sera of Patients With African T. Gambiense Trypanosomiasis , Ann Inst Pasteur 101:382-388, 1961;.
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