Abstract
The presence of immunoglobulins (Ig) in the circulation of normal humans and animals that bind a variety of foreign antigens, such as bacterial components and products, viruses, protozoa, fungi, as well as self antigens, such as nucleic acids, phospholipids, erythrocytes, serum proteins, cellular components, insulin and thy-roglobulin, has been recognized since the beginning of this century [1–9]. Because their emergence is independent of known and/or intentional immunization, these antibodies have been termed “natural antibodies”. In contrast to antigen-induced antibodies, which are mainly IgG and monoreactive, a considerable proportion of natural antibodies are IgM and polyreactive, that is they bind several unrelated antigens with different affinities. Natural polyreactive and monoreactive IgG and IgA antibodies also exist [7]. The vast majority of natural antibodies, whether IgM, IgG or IgA, are produced by CD5+ B cells, the predominant lymphocytes in the neonatal cell repertoire [10,11]. Because of their broad reactivity with a variety of microbial components, diese antibodies may play a major role in the primary line of defense against infections. Owing to their ability to bind self antigens, they may serve as templates for some of the high-affinity autoantibodies that emerge in patients with autoimmune disease, particularly those associated with a significant expansion of CD5+ B cells [12–14].
Keywords
- Systemic Lupus Erythematosus
- Chronic Lymphocytic Leukemia
- Natural Antibody
- Antigen Binding Activity
- Chain CDR3
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
Boyden S (1965) Natural antibodies and the immune response. Adv Immunol 5:1–28
Michael JG (1969) Natural antibodies. Curr Top Microbiol Immunol 48:43–62
Casali P, Notkins AL (1989) CD5+ B lymphocytes, polyreactive antibodies and the human B-cell repertoire. Immunol Today 10:364–368
Avrameas S (1991) Natural autoantibodies: from “horror autotoxicus” to “gnothi seauton.” Immunol Today 12:154–159
Riboldi P, Kasaian MT, Mantovani L, Ikematsu H, Casali P (1993) Natural antibodies. In: Bona CA, Siminovitch K, Zanetti M, Theophilopoulos AN (ed) Molecular Pathology of Autoimmunity. The Harwood Academic Publisher, New York, pp 45–64
Turman MA, Casali P, Notkins AL, Bach FH, Platt JL (1991) Polyreactive antibodies from CD5+ B cells: antigen specificity and relationship to xenoreactive natural antibodies. Transplantation 52:710–717
Kasaian MT, Ikematsu H, Casali P (1992) Identification and analysis of a novel human surface CD5-B lymphocyte subset producing natural antibodies. J Immunol 148:2690–2702
Kasaian MT, Casali P (1992) Analysis of the human CD5-CD45RAlo B cell subset. Ann NY Acad Sci 651:59–69
Nakamura M, Burastero SE, Notkins AL, Casali P (1988) Human monoclonal rheumatoid factor-like antibodies from CD5 (Leu-1+) B cells are polyreactive. J Immunol 140:4180–4186
Durandy A, Thuillier L, Forveille M, Fischer A (1990) Phenotypic and functional characteristics of human newborns’ B lymphocytes. J Immunol 144:60–65
Gadol N, Ault KA (1986) Phenotypic and functional characterization of human Leu 1 (CD5) B cells. Immunol Rev 95:23–34
Burastero SE, Casali P (1989) Characterization of human CD5 (Leu-1 OKT1)+ B lymphocytes and the antibodies they produce. Contrib Microbiol Immunol 11:231–262
Casali P, Notkins AL (1989) Probing the human B-cell repertoire with EBV: Polyreactive antibodies and CD5+ B lymphocytes. Ann Rev Immunol 7:513–535
Burastero SE, Casali P, Wilder RL, Notkins AL (1988) Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis. J Exp Med 168:1979–1992
Casali P, Kasaian MT, Haughton G (1994) B-l (CD5 B) cells. In: Coutinho A, Kazatchkine MD (ed) Autoimmunity: Physiology and Disease. John Wiley and Sons, Inc., New York, pp 57–88
Kasaian MT, Casali P (1993) Autoimmunity-prone B-l (CD5 B) cells, natural antibodies and self recognition. Autoimmunity 15:315–329
van Voorhis WC, Schlekewy L, Trong HL (1991) Molecular mimicry by Trypanosmoa cruzi: the Fl-160 epitope that mimics mammalian nerve can be mapped to a 12-amino acid peptide. Proc Natl Acad Sci USA 88:5993–5997
Lafer EM, Rauch J, Andrzejewski JR, Mudd D, Furie B, Schwartz RS, Stollar DB (1981) Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phos-pholipids. J Exp Med 153:897–909
Ikematsu H, Harindranath N, Notkins AL, Ueki Y, Casali P (1993) Clonal analysis of a human antibody response. II. Sequences of the VH genes of human monoclonal IgM, IgG and IgA to rabies virus reveal preferential utilization of the VHIH segments and somatic hypermu-tation. J Immunol 150:1325–1337
Ueki Y, Goldfarb I, Harindranath N, Gore M, Koprowski H, Notkins AL, Casali P (1990) Clonal analysis of a human antibody response: Quantitation of precursors of antibody-producing cells and generation and characterization of monoclonal IgM, IgG, and IgA to rabies virus. J Exp Med 171:19–34
Foote J, Milstein C (1991) Kinetic maturation of an immune response. Nature 352:530–532
Hayakawa K, Hardy RR, Honda M, Herzenberg LA, Steinberg AD, Herzenberg LA (1984) Ly-1 B cells: Functionally distinct lymphocytes that secrete IgM autoantibodies. Proc Natl Acad Sci USA 81:2494–2498
Engleman EG, Warnke R, Fox RI, Dilley J, Benike C, Levy R (1981) Studies of a human T lymphocyte antigen recognized by a monoclonal antibody. Proc Natl Acad Sci USA 78:1791–1795
Huang HJ, Jones NH, Strominger JL, Herzenberg LA (1987) Molecular cloning of Ly-1, a membrane gycoprotein of mouse T lymphocytes and a subset of B cells: Molecular homology to its human counterpart Leu-1/Tl (CD5). Proc Natl Acad Sci USA 84:204–208
Jones NH, Clabby ML, Dialynas DP, Huang, HJ, Herzenberg LA, Strominger JL (1986) Isolation of complementary DNA clones encoding the human lymphocyte glycoprotein Tl/Leu-1. Nature 323:346–349
Herzenberg LA, Stall AM, Lalor PA, Sidman C, Moore WA, Parks DR, Herzenberg LA (1986) The Ly-1 B cell lineage. Immunol Rev 93:81–102
Lalor PA, Herzenberg LA, Adams S, Stall AM (1989) Feedback regulation of murine Ly-1 B cell development. Eur J Immunol 19:507–513
Hayakawa K, Hardy RR (1988) Normal, autoimmune, and malignant CD5+ B cells: The Ly-1 B lineage? Ann Rev Immunol 6:197–218
Boumsell L, Bernard A, Lepage V, Degos L, Lemerle J, Dausset J (1978) Some chronic lym-phocytic leukemia cells bearing surface immunoglobulins share determinants with T cells. Eur J Immunol 8:900–904
Boumsell L, Coppin H, Pham D, Raynal B, Lemerle J, Dausset J, Bernard A (1988) An antigen shared by human T cell subsets and B cell chronic lymphocytic leukemia cells: Distribution on normal and malignant cells. J Exp Med 152:229–234
Royston I, Majoa JA, Baird SM, Meserve GL, Griffiths JC (1980) Human T-cell antigens defined by monoclonal antibodies: The 65,000-dalton antigen of T cells (T65) is also found on chronic lymphocytic leukemia cells bearing surface immunoglobulin. J Immunol 125:725–731
Caligaris-Cappio F, Gobbi M, Bofill M, Janossy G (1982) Infrequent normal B lymphocytes express features of B-chronic lymphocytic leukemia. J Exp Med 155:623–628
Gobbi M, Caligaris-Cappio F, Janossy G (1983) Normal equivalent of cells of B cell malignancies: Analysis with monoclonal antibodies. Brit J Haematol 54:393–403
Antin JH, Emerson SG, Martin P, Gadol N, Ault KA (1986) Leu-1+ (CD5+) B cells: A major lymphoid subpopulation in human fetal spleen: phenotypic and functional studies. J Immunol 136:505–510
Hayakawa K, Hardy RR, Herzenberg LA (1986) Peritoneal Ly-1 B cells: Genetic control, autoantibody production, increased lambda light chain expression. Eur J Immunol 16:450–465
Kipps TJ, Fong S, Tomhave E, Chen PP, Goldfien RD, Carson DA (1987) High frequency expression of a conserved kappa variable region gene in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 84:2916–2920
Casali P, Burastero SE, Nakamura M, Inghirami G, Notkins AK (1987) Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to the Leu-1+ B-cell subset. Science 236:77–81
Hayakawa K, Hardy RR, Parks DR, Herzenberg LA (1983) The “Ly-1 B” cell subpopulation in normal, immunodefective, and autoimmune mice. J Exp Med 157:202–218
Hasegawa K, Nishimura H, Ogawa S, Hirose S, Sato H, Shirai T (1990) Monoclonal antibodies to epitope of CD45R(B220) inhibit interleukin 4-mediated B cell proliferation and differentiation. Internat Immunol 2:367–375
Mittler RS, Greenfield RS, Schacter BZ, Richard NF, Hoffmann MK (1987) Antibodies to the leukocyte antigen (T200) inhibit an early phase in the activation of resting human B cells. J Immunol 138:3159–3166
Yakura H, Kawabata I, Ashida T, Katagiri M (1988) Differential regulation by Ly-5 and Lyb-2 of IgG production induced by lipopolysaccharide and B cell stimulatory factor-1 (IL-4). J Immunol 141:875–880
Yakura H, Kawabata I, Shen FW, Katagiri M (1986) Selective inhibition of lipopolysac-charide-induced polyclonal IgG response by monoclonal Ly-5 antibody. J Immunol 136:2729–2733
Yakura H, Shen FW, Bourcet E, Boyse EA (1983) On the function of Ly-5 in the generation of antigen-driven B cell differentiation. Comparison and contrast with Lyb-2. J Exp Med 157:1077–1088
Kantor AB (1991) The development and repertoire of B-l cells (CD5 B cells). Immunol Today 12:389–391
Matsuda F, Shin EK, Nagaoka H, Matsumura R, Haino M, Fukita Y, Takaishi S, Imai T, Riley JH, Anand R, Soeda E, Honjo T (1993) Structure and physical map of 64 variable segments in the 3’ 0.8-megabase region of the human immunoglobulin heavy-chain locus. Nature Genet 3:88–94
Cook GP, Tomlinson IM, Walter G, Riethman H, Carter NP, Buluwela L, Winter G, Rabbitts TH (1994) A map of the human immunoglobulin VH locus completed by analysis of the telomeric region of chromosome 14q. Nature Genet 8:162–168
Ikematsu H, Ichiyoshi Y, Schettino EW, Nakamura M, Casali P (1994) VH and VK segment structure of anti-insulin IgG autoantibodies in patients with insulin-dependent diabetes melli-tus. Evidence for somatic selection. J Immunol 152:1430–1441
Ikematsu H, Kasaian MT, Schettino EW, and Casali P (1993) Structural analysis of the VH-D-JH segments of human polyreactive IgG mAb. Evidence for somatic selection. J Immunol 151:3604–3616
Kasaian MT, Ikematsu H, Balow JE, Casali P (1994) Structure of the VH and VL segments of monoreactive and polyreactive IgA autoantibodies to DNA in patients with systemic lupus erythematosus. J Immunol 152:3137–3151
Mantovani L, Wilder RL, Casali P (1993) Human rheumatoid B-la (CD5+ B) cells make so-matically hypermutated high affinity IgM rheumatoid factors. J Immunol 151:473488
Kasaian MT, Casali P (1995) B-l cellular origin and VH segment strucutre of IgG, IgA, and IgM anti-DNA autoantibodies in patients with systemic lupus erythematosus. Ann NY Acad Sci In press
Colman PM (1988) Structure of antibody-antigen complexes: Implications for immune recognition. Adv Immunol 43:99–132
Kabat EA (1988) Antibody complementarity and antibody structure. J Immunol (suppl) 141:S25–S36
Amit AG, Mariuzza RA, Phillips SE, Poliak RJ (1986) Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution. Science 233:747–753
Stanfield RL, Fieser TM, Lerner RA, Wilson IA (1990) Crystal structure of an antibody to a peptide and its complex with peptide antigen at 2.8 A. Science 248:712–719
Eilat D, Webster DM, Rees AR (1988) V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW Fl mice. J Immunol 141:1745–1753
Shlomchik M, Mascelli M, Shan H, Radic MZ, Pisetsky D, Marshak-Rothstein A, Weigert MG (1990) Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic point mutation. J Exp Med 171:265–292
Casali P, Nakamura M, Ginsberg-Fellner F, Notkins AL (1990) Frequency of B cells committed to the production of antibodies to insulin in newly diagnosed patients with insulin-dependent diabetes mellitus and generation of high affinity monoclonal IgG to insulin. J Immunol 144:3741–3747
Ichiyoshi Y, Zhou M, Casali P (1995) A human anti-insulin IgG autoantibody apparently arises through clonal selection from an insulin-specific “germ-line” natural antibody template. J Immunol 154:226–238
Ichiyoshi Y, Casali P (1994) Analysis of the structural correlates for antibody polyreactivity by multiple reassortments of chimeric human immunoglobulin heavy and light chain V segments. J Exp Med 180:885–895
Kipps TJ, Robbins BA, Carson DA (1990) Uniform high frequency expression of autoanti-body-associated crossreactive idiotypes in the primary B cell follicles of human fetal spleen. J Exp Med 171:189–196
Pisetsky DS, Jelinek DF, McAnally LM, Reich CF, Lipsky PE (1990) In vitro autoantibody production by normal adult and cord blood B cells. J Clin Invest 85:899–903
Lydyard PM, Quartey-Papafio R, Broker B, Mackenzie L, Jouquan J, Blaschek MA, Steele J, Petrou M, Collins P, Isenberg D, Youinou PY (1990) The antibody repertoire of early human B cells: I. High frequency of autoreactivity and polyreactivity. Scand J Immunol 31:33–43
Herzenberg LA, Herzenberg LA (1989) Toward a layered immune system. Cell 59:953–954
Dauphinee M, Tovar Z, Talal N (1988) B cells expressing CD5 are increased in Sjogren’s syndrome. Arthritis Rheum 31:642–647
Velasquillo MC, Alcocer-Varela J, Alarcon-Segovia D, Cabiedes J, Sanchez-Guerrero J (1991) Some patients with primary antiphopholipid syndrome have increased circulating CD5+ B cells that correlate with levels of IgM antiphospholipid. Clin Exp Rheum 9:1–5
Harindranath N, Goldfarb IS, Ikematsu H, Burastero SE, Wilder RL, Notkins AL, Casali P (1991) Complete sequence of the genes encoding the VH and VL regions of low-and high-affinity monoclonal IgM and IgAl rheumatoid factors produced by CD5+ B cells from a rheumatoid arthritis patient. Int Immunol 3:865–875
Suzuki N, Sakane T, Engleman EG (1990) Anti-DNA antibody production by CD5+ and CD5-B cells of patients with systemic lupus erythematosus. J Clin Invest 85:238–247
Mannheimer-Lory A, Katz JB, Pillinger M, Ghossein C, Smith A, Diamond B (1991) Molecular characteristics of antibodies bearing an anti-DNA-associated idiotype. J Exp Med 174:1639–1652
Dersimonian H, Schwartz RS, Barrett KJ, Stollar DB (1987) Relationship of human variable region heavy chain germ-line genes to genes encoding anti-DNA autoantibodies. J Immunol 139:2496–2501
van Es JH, Gmelig-Meyling FHJ, van de Akker WRM, Aanstoot H, Derksen RHWM, Logtenberg T (1991) Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systemic lupus erythematosus. J Exp Med 173:461–470
Diamond B, Katz JB, Paul E, Aranow C, Lustgarten D, Scharff MD (1992) The role of somatic mutation in the pathogenic anti-DNA response. Ann Rev Immunol 10:731–757
Bos, NA, Kimura H, Meewsen CG, De Visser H, Hazenberg MP, Wostmann BS, Pleasants JR, Benner R, Marcus DM (1989) Serum immunoglobulin levels and naturally occurring antibodies against carbohydrate antigens in germ-free BALB/c mice fed chemically defined ul-trafiltered diet. EUT J Immunol 19:2335–2339
Underwood JR, Pederson JS, Chalmers PJ, Toh BH (1985) Hybrids from normal, germ-free, nude and neonatal mice produce monoclonal autoantibodies to eight different intracellular structures. Clin Exp Immunol 60:417–426
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Springer-Verlag Berlin Heidelberg
About this paper
Cite this paper
Casali, P., Schettino, E.W. (1996). Structure and Function of Natural Antibodies. In: Potter, M., Rose, N.R. (eds) Immunology of Silicones. Current Topics in Microbiology and Immunology, vol 210. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-85226-8_17
Download citation
DOI: https://doi.org/10.1007/978-3-642-85226-8_17
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-642-85228-2
Online ISBN: 978-3-642-85226-8
eBook Packages: Springer Book Archive