Endogenous humoral autoreactive immune responses to apoptotic cells: Effects on phagocytic uptake, chemotactic migration and antigenic spread

Joy Das, Pooja Arora, Donald Gracias, Alagangula Praveen, Beena P J Raj, Elishba Martin, Rahul Pal

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Enhanced cell death and deficient clearance of cellular debris are thought to contribute to increased self-antigen exposure in systemic autoimmune disease. To investigate the characteristics of early humoral autoimmune responses, six monoclonal antibodies were generated from two autoimmune prone strains of mice. All antibodies specifically bound the surface of late-stage apoptotic cells. Similar antibody reactivities were present in the sera of patients with systemic lupus erythematosus. While IgM antibodies significantly reduced the phagocytic uptake of apoptotic thymocytes, IgG antibodies enhanced uptake. Poly-reactivity was demonstrated in the recognition of ribonucleoproteins and lipids. An antibody reactive towards lysophosphatidylcholine reversed lysophosphatidylcholine-mediated inhibition of LPS-induced TNF-α production and adversely affected the transmigration of phagocytes towards an apoptotic stimulus. In several instances, CDR were characterized by the accumulation of somatic mutations. Anti-idiotypic antibodies generated upon immunization bound distinct cellular moieties and self-antigens. Poly-specific, apoptotic cell-reactive autoantibodies can therefore directly impact upon the course of disease by influencing phagocytic uptake of apoptotic cells, by inducing a proinflammatory environment through neutralization of bioactive lipids, by blinding phagocytes to the presence of dying cells through the negation of lipidic chemotactic signals, and by mediating diversification of the humoral autoimmune response via the idiotypic network.

Original languageEnglish (US)
Pages (from-to)3561-3574
Number of pages14
JournalEuropean Journal of Immunology
Volume38
Issue number12
DOIs
StatePublished - 2008
Externally publishedYes

Fingerprint

Humoral Immunity
Antibodies
Lysophosphatidylcholines
Autoantigens
Phagocytes
Autoimmunity
Lipids
Ribonucleoproteins
Thymocytes
Systemic Lupus Erythematosus
Autoantibodies
Autoimmune Diseases
Immunoglobulin M
Anti-Idiotypic Antibodies
Immunization
Cell Death
Immunoglobulin G
Monoclonal Antibodies
Serum

Keywords

  • Apoptosis
  • Autoimmunity
  • Systemic lupus erythematosus

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Endogenous humoral autoreactive immune responses to apoptotic cells : Effects on phagocytic uptake, chemotactic migration and antigenic spread. / Das, Joy; Arora, Pooja; Gracias, Donald; Praveen, Alagangula; Raj, Beena P J; Martin, Elishba; Pal, Rahul.

In: European Journal of Immunology, Vol. 38, No. 12, 2008, p. 3561-3574.

Research output: Contribution to journalArticle

Das, Joy ; Arora, Pooja ; Gracias, Donald ; Praveen, Alagangula ; Raj, Beena P J ; Martin, Elishba ; Pal, Rahul. / Endogenous humoral autoreactive immune responses to apoptotic cells : Effects on phagocytic uptake, chemotactic migration and antigenic spread. In: European Journal of Immunology. 2008 ; Vol. 38, No. 12. pp. 3561-3574.
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