Description
General Description
Factor Ba is the fragment of complement factor B that results from activation of the alternative pathway. CompTech prepares the factor Ba fragment from
factor B which was purified from normal human serum. Complement factor B is a glycosylated protein composed of a single 93,000 Da polypeptide chain. Factor B is an
essential component of the alternative pathway of complement activation and is found in plasma at approximately 200 µg/mL. In the presence of Mg++ factor B binds to C3b and
the C3b,B complex can be activated by factor D, a serine protease that circulates as an active trypsin-like serine protease. Cleavage of factor B by factor D causes the release of
the Ba fragment (33,000 Da) and leaves the 60,000 Bb fragment bound to C3b. This Ba fragment comes from the N-terminal of factor B and it contains three CCP domains
which interact with C3b (Morley, B.J. and Walport, M.J. (2000)). The isolated fragment Ba has been reported to have a weak affinity for C3b and to inhibit the interaction of
factor B with C3b thus inhibiting the activation of the alternative pathway (Pryzdial, E.L. and Isenman, D.E., (1987)).
The fragments of factor B (Ba and Bb) have been proposed to elicit several biological responses. See the section titled Function below and in the product description for the Bb fragment.
Physical Characteristics & Structure
Molecular weight: 33,000 Daltons, single chain protein containing carbohydrate (Rother, K. et al. (1998); Morley, B.J. and Walport, M.J. (2000)). The protein is
negatively charged at serum pH. The Ba fragment contains the three CCP domains of factor B while the Bb fragment, contains the active serine protease site of C3b,Bb.
Crystal structures for the serine protease domain at 2.1 angstrom resolution (Jing, H. et al. (2000)), the Ba domain (Milder, F.J. et al. (2007)) and the whole protein (Bhattacharya,
A.A. et al. (2004)) at 2.3 angstrom resolution have been published.
Function
The fragments of factor B (Ba and Bb) have been proposed to elicit numerous biological responses; however, many of these activities have proved to be controversial
with an inconsistent record of reproducibility. It is not yet clear whether these failures are due to different experimental conditions, more highly purified Ba and Bb than
available in the early days or the need to test fresh, in situ-prepared fragments, as has been suggested.
Both fragments Ba and Bb have been reported to bind to B lymphocyte receptors and modulate proliferation (Kolb, W.P., et al. (1989)). Ba, but not Bb, was shown to
exhibit growth-supporting activity for activated murine B lymphocytes (Praz, F. and Ruuth, E. (1986)). On the other hand, Ba has been reported to inhibit human B cell
proliferation (Ambrus, J.L. et al. (1990)). The small fragment Ba has been reported to show chemotactic activity with neutrophils and macrophages, but this effect is so much
lower than that of C5a or even C5adesArg that its effect in vivo may be negligible (Morgan, B.P., (1990)). In a study of smooth muscle contractile activity, neither Ba nor
Bb caused contraction of guinea pig ileum (a sensitive test for C5a) or histamine release from rat mast cells, but Ba caused guinea pig PMN to increase chemotactic activity
(Hamuro, J., et al. (1978)).
Assays
There are no convenient assays for the biological activity of Ba. Several companies produce ELISA kits for measuring Ba levels in blood samples (Dodds, A.W. and Sim, R.B. (1997)).
Applications
Split products of factor B in plasma are indicative of activation of the alternative pathway in vivo. ELISA kits for measurement of Ba and Bb are commercially available.
These have been used in numerous human and animal studies (Lynch, A.M., et al. (2008)). See In vivo section below.
In vivo
The average concentration of factor B in blood is 200 µg/mL (range 170-258 µg/mL) in human plasma. Factor B is an acute phase protein whose plasma levels
increases during inflammation. The fragments Ba and Bb are released upon activation of the alternative pathway and circulate in blood until cleared (Lynch, A.M., et al. (2008)).
Baseline levels in normally have been reported to be 29 ng Ba/mL (0.015% of the factor B concentration). The concentration of fragment Ba in patients with tubular proteinuria
was found to be elevated more than 100-fold (4800 ng/mL)(Opperman, M. et al. (1991)). There was a minimal increase in the plasma concentration of fragment Bb in these patients.