On 2015 Sep 28, Donald Forsdyke commented:

General Principle of Juxtaposition- and Concentration-Dependent Activation of Complement

Seeking to understand "immune system … ability to discriminate self from nonself," the authors here describe an elegant “clustering-based mechanism” for complement activation by MBL that is “akin to the mechanism governing signaling through many cellular receptors,” and distinguishes the lectin and classical pathways of complement activation (1). Their demonstration of the general principle of “juxtaposition- and concentration-dependent activation,” is in keeping with studies with the MBL, concanavalin-A, that were reported in 1977 (2).

However, the latter studies were not mentioned (1), and a new review states that “the ‘lectin pathway’ was discovered in the early 1980s” (3). Thus, it is possible that those engaged in this fascinating field are unaware of the earlier work that began to be reported in 1970 (4). Subsequent studies in the 1970s (5-8) culminated in demonstration of “the importance of the sequence of binding events” (9). It is to be hoped that the full relationship of our earlier work to modern studies will be determined in future work.

(1) Degn SE, et al. (2014) Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes. Proc. Natl. Acad. Sci. USA 111:13445-13450.

(2) Forsdyke DR (1977) Role of receptor aggregation in complement-dependent inhibition of lymphocytes by high concentrations of concanavalin-A. Nature 267:358-360. Forsdyke DR, 1977

(3) Thielens NM, Gaborlaud C, Thiel S (2015) Complement: classical and lectin pathways. In: eLS John Wiley & Sons, Chichester.

(4) Milthorp P, Forsdyke DR (1970) Inhibition of lymphocyte activation at high ratios of concanavalin A to serum depends on complement. Nature 227:1351-1352. Milthorp P, 1970

(5) Milthorp P, Forsdyke DR (1973) Serum factors affecting the incorporation of (3H)uridine by lymphocytes stimulated by concanavalin A. Studies of the role of complement. _Biochem. J. 132:803-812.Milthorp P, 1973

(6) Milthorp P, Forsdyke DR (1973) A comparison of the activation of thymus and lymph-node cells by concanavalin A and phytohaemagglutinin. Effects of complement. J. Immun. Meth. 2:269-277.Milthorp P, 1973

(7) Forsdyke DR (1978) Role of complement in the toxicity of dietary legumes. Med. Hypoth. 4:97-100 Forsdyke DR, 1978

(8) Forsdyke DR, Milthorp P (1979) Early onset inhibition of lymphocytes in heterologous serum by high concentrations of concanavalin-A. Further studies of the role of complement with suramin and heated serum. Int. J. Immunopharmacol. 1:133-139.Forsdyke DR, 1979

(9) Forsdyke DR (1980) Lectin pulses as determinants of lymphocyte activation and inactivation during the first six hours of culture: sequential action of concanavalin-A and complement cause cell lysis. Can. J. Biochem. 58:1387-1396. Forsdyke DR, 1980

On 2015 Sep 28, Donald Forsdyke commented:

General Principle of Juxtaposition- and Concentration-Dependent Activation of Complement

Seeking to understand "immune system … ability to discriminate self from nonself," the authors here describe an elegant “clustering-based mechanism” for complement activation by MBL that is “akin to the mechanism governing signaling through many cellular receptors,” and distinguishes the lectin and classical pathways of complement activation (1). Their demonstration of the general principle of “juxtaposition- and concentration-dependent activation,” is in keeping with studies with the MBL, concanavalin-A, that were reported in 1977 (2).

However, the latter studies were not mentioned (1), and a new review states that “the ‘lectin pathway’ was discovered in the early 1980s” (3). Thus, it is possible that those engaged in this fascinating field are unaware of the earlier work that began to be reported in 1970 (4). Subsequent studies in the 1970s (5-8) culminated in demonstration of “the importance of the sequence of binding events” (9). It is to be hoped that the full relationship of our earlier work to modern studies will be determined in future work.

(1) Degn SE, et al. (2014) Complement activation by ligand-driven juxtaposition of discrete pattern recognition complexes. Proc. Natl. Acad. Sci. USA 111:13445-13450.

(2) Forsdyke DR (1977) Role of receptor aggregation in complement-dependent inhibition of lymphocytes by high concentrations of concanavalin-A. Nature 267:358-360. Forsdyke DR, 1977

(3) Thielens NM, Gaborlaud C, Thiel S (2015) Complement: classical and lectin pathways. In: eLS John Wiley & Sons, Chichester.

(4) Milthorp P, Forsdyke DR (1970) Inhibition of lymphocyte activation at high ratios of concanavalin A to serum depends on complement. Nature 227:1351-1352. Milthorp P, 1970

(5) Milthorp P, Forsdyke DR (1973) Serum factors affecting the incorporation of (3H)uridine by lymphocytes stimulated by concanavalin A. Studies of the role of complement. _Biochem. J. 132:803-812.Milthorp P, 1973

(6) Milthorp P, Forsdyke DR (1973) A comparison of the activation of thymus and lymph-node cells by concanavalin A and phytohaemagglutinin. Effects of complement. J. Immun. Meth. 2:269-277.Milthorp P, 1973

(7) Forsdyke DR (1978) Role of complement in the toxicity of dietary legumes. Med. Hypoth. 4:97-100 Forsdyke DR, 1978

(8) Forsdyke DR, Milthorp P (1979) Early onset inhibition of lymphocytes in heterologous serum by high concentrations of concanavalin-A. Further studies of the role of complement with suramin and heated serum. Int. J. Immunopharmacol. 1:133-139.Forsdyke DR, 1979

(9) Forsdyke DR (1980) Lectin pulses as determinants of lymphocyte activation and inactivation during the first six hours of culture: sequential action of concanavalin-A and complement cause cell lysis. Can. J. Biochem. 58:1387-1396. Forsdyke DR, 1980