Re: Why is C2a called C2a not C2b?

Hi Amr,

The central issue in your question stems from discrepancies in the nomenclature for naming the fragments of the complement C2 protein. For most of the proteolytically cleaved complement proteins, the smaller fragment is given an 'a' suffix, and the larger fragment is given a 'b' suffix. This is illustrated in the following illustration of the classical and alternative complement pathways (from the Wikipedia entry on the complement system).

However, some references use 'C2a' to refer to the larger C2 fragment, while others use 'C2b' to refer to the larger fragment. This is because the larger C2 fragment was called C2a in the original paper characterizing the fragments. By 1994 the current nomenclature had been widely-accepted, so that the larger C2 fragment was denoted as C2b. So, it is now incorrect to say that at C2a is the larger C2 fragment. Unfortunately, some resources still use the older nomenclature for C2 fragments, confusing the issue.

In an attempt to understand why the larger C2 fragment was named C2a instead of C2b, I took a look at the Michael A. Kerr's 1979 paper that first described the proteolytic cleavage of complement components C2 and factor B into peptide fragments C2a and C2b and Ba and Bb. You can read this paper yourself on Pubmed Central.

Note, that Kerr uses Ba and Bb to denote the smaller and larger fragments of the factor B protein; while this may be in keeping with the current nomenclature, it is clear that there was not any nomenclature in force when this work was published. Also, the paper provides no rationale for denoting one fragment of C2 or B as the 'a' or 'b' fragment. I think that this means that there was a very simple and straightforward rationale for the naming of each fragment.

If you look at Figure 2 and Figure 4 in Kerr's paper, I think that you will see that very straightforward reason why the fragments are named 'a' or 'b'. Both figures are chromatographs showing the absorbance at 280 nanometers (A₂₈₀, which is a handy wavelength for detecting the presence of protein) over the fractions of digested C2 and B proteins eluted from a Sephadex column. There are two clear absorbance peaks Figure 2, which shows the fractionation of the C2 digest, indicating one peptide fragment in fractions 110 to 120 ml, and a second fragment in fractions 125 to ~138 ml. The first fragment to come off of the column is described as being in "pool A", and the second as being in "pool B". SDS-PAGE indicates that the fragment in pool A is larger than the fragment in pool B. So, I think that the larger C2 fragment was originally named C2a because it came off of the Sephadex column first!

Compare this to Figure 4, which shows the fractionation of the factor B digest. In that experiment, it is the smaller fragment that elutes first, and therefore the smaller fragment is named Ba, while the larger fragment is named Bb.

So, the naming of the C2 and B fragments as either a or b was (very likely) originally unrelated to their functions in the complement pathway, and depended on how fast they migrated through a Sephadex column.

Keep asking questions!

Here are the sources that I referred to above.

Kerr MA. (1979) Limited proteolysis of complement components C2 and factor B. Structural analogy and limited sequence homology. Biochem J. 183(3):615- 22.

Janeway C, Travers P (1994). Immunobiology : The Immune System in Health and Disease. London; San Francisco; New York: Current Biology Limited; Garland Pub. Inc.
ISBN 0815316917