| Topic | Overview |
| Isotype Switching | T cell help through the CD40/CD40L interaction is required for isotype switching. The FLOW patterns show that expression of CD40 and CD40 L appears normal. Expression of AID is also required for isotype switching.
If there is an I region present: The defect could be in CD40 or CD40L: an interaction between them is required to isotype switch. The defect could be an overproduction of IFN-γ which blocks DNA rearrangement (switching). The defect could not be in IL-4 or its receptor since there is transcription of the unrearranged gene. If there is no I region present: then it must be AID protein (if no transcripts are formed and no Ig is present). |
| T Cell | If all you know is that T cells are not functioning — or maybe not mounting a secondary response — then a good defect candidate is CD40L. |
| No Antibodies | If they are not rearranging, that is the likely cause of no expression. If they are rearranging, there is a defect in something required for surface expression: candidates are the membrane exon of the heavy chain, Ig-α, Ig-β, or surrogate light chain; or proteins required to transport the antibody to the surface. |
| No Rearrangement | Frequently caused by lack of RAG enzymes leading to no antibody production and no T cell maturation (arrested at DN stage). |
| CD40/CD40L | Needed for isotype switching. |
| IgG1/IgE deficiency | A selective decrease in IgG1 and IgE is observed. The most likely expanation is a defect in IL-4 (or IL-4R) or possibly an increase in IFN-γ because these selectively impact these isotypes. Since IgG2 and IgG3 remain essentially unchanged it does not appear to be a general defect such as CD40 or CD40L. |
