Anti-j: Human Cold Agglutinins Recognizing Linear (i) and Branched (I) Type 2 Chains

Abstract

Two IgMa cold agglutinins (CAs) reacted with protease- and sialidase-resistant antigens expressed in equal strength on human adult (I), newborn (i), i adult, rabbit (I) and rhesus monkey (i) erythrocytes. The antibodies were inhibited by the linear type 2 sequence lacto-N-neotetraose and the branched type 2 sequence lacto-N-neohexaose. Endo-ß-galactosidase treatment of red cells, which splits type 2 chains from the surface, abolished CA reactivity. The CAs expressed the idiotype recognized by the anti-idiotype 9G4 specific for anti-I and anti-i CAs. The data suggest that the two CAs recognize linear (i) as well as branched (I) type 2 chains. It is proposed to term these CAs anti-j.

A new cold autoagglutinin specificity: the third external loop of band 3

“…Cold autoagglutinins (CAs) are almost always of immunoglobulin (Ig)M class and directed to a variety of target antigens 1 . Anti‐I, anti‐i, anti‐j(I+i), and anti‐Pr are the most common specificities 2‐5 . In addition to Pr determinants, five other sialic acid–containing receptors, Sia‐b1, Sia‐l1, Sia‐lb (formerly Fl,Vo,Gd), Sa, and Lud, were recognized through the careful serologic investigation of scarce CAs 1,6‐8 .…”

The Immunoglobulin V(H) Gene, V(H)4-21, Specifically Encodes Autoanti-Red Cell Antibodies against the I or i Antigens

“…A survey of the reactivity of the MoAb with a panel of paraproteins from patients with macroglobulinaemia without CA activity (18 sera) revealed that none were positive [10], again linking the gene product with functional antibodies. Also, among a random panel of 55 paraproteins from patients with myeloma, no reactivity with the MoAb was detected, indicating low usage of the VH4-21 gene in these tumours [10], Less is known about the VH gene usage by other autoantired cell antibodies, although one anti-Pr2 antibody has been found to be encoded by a member of the VH1 family [12], More recently, we have found that several autoantibodies specific for sialylated carbohydrate antigens do not react with the MoAb [3], These findings raised the possibility that the MoAb might be useful in discriminating between autoantibodies against various red cell antigens, and there fore provide confirmation of anti-Ii specificity.…”

“…chains [3], The I, i and j antigens are resistant to treatment with either proteases or sialidase. The other two groups of red cell antigens are variously susceptible to digestion with proteases or sialidase; one group includes the Pr and Sa anti gens, and the other the sialidase-sensitive Sia-11-, -bl and -Ibi, previously termed Vo, FI and Gd [1], Discrimination of autoantibody specificities for these different antigens cur rently requires careful assessment of agglutination patterns with enzyme-treated red cells, and lack of reproducibility between laboratories may hinder classification.…”

The Immunoglobulin VH Gene, VH4–21, Specifically Encodes Autoanti‐Red Cell Antibodies against the I or i Antigens

“…Less is known about the V, gene usage by other autoantired cell antibodies, although one anti-Pr2 antibody has been found to be encoded by a member of the Y.,l family [12]. More recently, we have found that several autoantibodies specific for sialylated carbohydrate antigens do not react with the MoAb [3]. These findings raised the possibility that the MoAb might be useful in discriminating between autoantibodies against various red cell antigens, and therefore provide confirmation of anti-Ii specificity.…”

“…The majority of CA recognise the i and I carbohydrate antigens; these are developmentally regulated antigens, with the i antigen, a linear poly-N-acetyl lactosamine, being detected on cord red cells, and the I antigen, which contains branched chains, being synthesized after birth. The j antigen defines a recently described specificity since the antigen is expressed in equal strength on adult(I), newborn(i) and i adult cells and appears to consist for both linear (i) and branched (I) type 2 chains [3]. The I, i and j antigens are resistant to treatment with either proteases or sialidase.…”