Functional Properties of Heterogeneous Human Asialo-C4 and Its Isotypes C4A and C4B

Duane R. Schultz, Patricia I. Arnold

Research output: Contribution to journalArticle

Abstract

The fourth component of human complement (C4) is encoded at two separate but closely linked loci within the MHC on the short arm of chromosome 6. Thus, there are two types of C4 protein in most individual and pooled normal human sera (NHS): C4A and C4B. Incubation of individual sera, pooled NHS, or purified heterogeneous C4 (C4A/C4B) with bacterial sialidase at 37°C increased C-mediated hemolysis of antibody-sensitized sheep erythrocytes 1.54- to 1.93-fold. Comparative studies of T(max) of human C2, using asialo-C4 or buffer-treated C4 on EAC1̄(gp) and extrapolation to time 0 indicated a Z value 4-fold higher with asialo-C4 This indicated that more hemolytically active C4̄2̄ complexes are available with sialidase-treated C4 compared to untreated C4. There was no appreciable difference in the % 125I-C4 bound to EAC1̄(gp) (sialidase- or buffer-treated). Sera from two different blood donors with C4A3 phenotype (C4BQ0), two different donors with C4B1 phenotype (C4AQ0), and serum from an individual heterozygous deficient at both C4A3 and C4B1 regions (A3, AQ0; B1, BQ0) were investigated. The C4 allotypes, purified from these sera, were treated with sialidase; the C4A3 was enhanced in hemolytic assays by sialidase-treatment (1.52- to 2.3-fold), whereas the C4B1 allotype was not enhanced. Fluorometric determinations revealed that approximately the same percentage of sialic acid was released from sialidase treated C4A3 and C4B1. Therefore, the increase in hemolytic titer observed after treatment of NHS or purified heterogeneous C4 with sialidase is a property of C4A3 but not a property of C4B1.

Original languageEnglish (US)
Pages (from-to)90-102
Number of pages13
JournalImmunobiology
Volume185
Issue number1
DOIs
StatePublished - Jan 1 1992

Keywords

  • (A) containing complement = (C) components {ieEAC1gp, EAC1gp,4bhu} (C4b is the major cleavage fragment of human C4), {ieEAC1gp,4bhu,2ahu} (C2a is the major cleavage fragment of human C2), a suprabar indicates the component is activated
  • (NHS) a + symbol next to a component indicates it was treated with sialidase (e.g., C4b+)
  • C4A, C4B
  • C4A3, C4B1
  • DGVB
  • E
  • SA
  • Sheep erythrocytes
  • allotypes of C4A and C4B
  • glucose gelatin Veronal buffer with calcium and magnesium, T of C2, time at which there is maximum formation of {ieEAC1gp,4bhu,2ahu} as determined by hemolysis after adding a C3 and C5–C9 mixture
  • isotypes of C4
  • normal human serum
  • sensitized with rabbit IgG antibody
  • sialic acid

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Hematology

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