What is the difference between heavy chain anti-IgG and light chain anti-IgG? Which is better to use?

I thought that light chains were either kappa or lambda, whatever the Ig class (but beware - I am no Immunologist)?

What is the difference between heavy chain anti-IgG and light chain anti-IgG? Which is better to use?

I'm not quite sure what do you mean by 'use'. However, I'm doing my best.

Every immunoglobulin (Ig) has heavy chains and light chains. As Malcolm said, the light chains can be either kappa or lambda. Heavy chains can be gamma, mu, alpha, epsilon or delta which determine whether the Ig will be IgG, IgM, IgE, IgA or IgD respectively.

However, I think in blood transfusion, it's more important to mention about Fc (Fragment crystalline) and Fab (Fragment antigen binding) parts of Ig rather than light chains and heavy chains. Fab which consists of variable and constant domains of both light chains and heavy chains. A hypervariable region on Fab is responsible for recognizing antigen (exactly it's epitope on antigen). Fc is composed of just constant domains of heavy chains. Fc is the part which is recognized by phagocytes (by Fc-receptor on the cells). Therefore, the target cell which carry the corresponding antigen will be destroyed by phagocytes.

Moreover, on Fc portion of IgG and IgM, there are receptors for complement to bind to. This explains why IgG and IgM can activate complement cascade whist other classes of Ig cannot.

Cheers

Han

I would assume that the difference between heavy chain anti-IgG and light chain anti-IgG would be what portion of the molecule the antibody is directed against. I think the the light chain portion is either the same or very similar between the different types of Ig (as Han explained). Therefore an antibody directed against light chain elements would perhaps be less specific than one directed against the heavy chain elements (which is the part that distinguishes the different forms of Ig).

Hi Jessi and Adiescast (Jessi, hopefully I understand your question correctly now

For anti-IgG, the antibody will recognize the Fc (as I mentioned, it is composed of constant domains heavy chains) of IgG rather than Fab.

Fab's function is to recognize epitope on antigen (rather than to be recognized by anti-Ig). Moreover, every specific clone of antibodies is determined by the Fab. It means, different clone of Abs will have different Fab 'configuration'. In fact, we don't have specific anti-IgG which is just used to detect a particular clone of IgG. Once it's called anti-IgG, it will detect any IgG irrespective of its clone. This explains why anti-IgG directs against Fc because Fc is similar for every IgG molecule.

Moreover, Fab is different while Fc is quite similar between individuals in the population. Therefore, the anti-IgG is produced against the Fc part of IgG. For example, rabbit IgG can be used as anti-human globulin because rabbit IgG recognize human Fc as foreign. Moreover, for this reason, the anti-IgG reagent can be applied for any IgG from every patient and there is no difference between individuals.

I don't know if my answer hit the point. Just hope

Cheers

Han

Thanks Han! That is what I was trying to say and I think you said it well.

Thank you for your excellent explanation, Han! Great job!

Your explanation made me visualize the old Ortho books that had "pictures" of huge red cells with IgG antibodies attached to the antigens sites on the red cells, then a picture of the rabbit Anti-IgG Antihuman Globulin attached to the Fc (ie: long arms) of the IgG molecules (resulting in agglutination.)

Dear Jessi

While all the comments above are absolutely correct I suspect (forgive me everyone if I am wrong) that they do not give you the answer you are looking for. The box inserts of most Coombs reagents which contain anti-IgG as a component will say something about whether the reagent is heavy or light chain specific. The difference is that those that are NOT heavy chain specific will also cross react to some degree with antibodies that are IgA or IgM in nature. On the other hand, an anti-IgG that IS heavy chain specific will ONLY react with antibodies that are IgG. To my knowledge most 'routine' coombs reagents are of the first type, as this will allow you to pick up an IgA-only DAT causing an auto-immune haemolytic anaemia, for example. On the other hand, monospecific Coombs reagents used for elucidating the nature of a positive DAT are usually of the second type (maybe not if its only to distinguish between IgG or complement - but should be if it's to distinguish between IgG and IgA, for example). If it does not specify in the box insert of the Coombs reagent you are using, the manufacturer of the reagent should be able to tell you which it is.