Elderly humans have compromised humoral and cellular immune responses, which lead to reduced protection to infectious agents and to vaccines. Currently, available vaccines suboptimally protect the elderly population. The capacity to class switch the Ig H chain is critical to the effectiveness of humoral immune responses in mice and humans. We have previously shown in mice that the E2A-encoded t...

Somatic hypermutation of immunoglobulin (Ig) genes occurs at a frequency that is a million times greater than the mutation in other genes. Mutations occur in variable genes to increase antibody affinity, and in switch regions before constant genes to cause switching from IgM to IgG. Hypermutation is initiated in activated B cells when the activation-induced deaminase protein deaminates cytosine...

Somatic hypermutation of immunoglobulin (Ig) genes occurs at a frequency that is a million times greater than the mutation in other genes. Mutations occur in variable genes to increase antibody affinity, and in switch regions before constant genes to cause switching from IgM to IgG. Hypermutation is initiated in activated B cells when the activation-induced deaminase protein deaminates cytosine...

Intravenous immunoglobulin (IVIg) therapy may be considered medically necessary for the following indications.  Immunodeficiency States—patients with Primary Immunodeficiencies, including o Congenital agammaglobulinemia o Hypogammaglobulinemia o Common variable immunodeficiency o Severe combined immunodeficiency (SCID) o Wiskott-Aldrich syndrome o X-linked agammaglobulinemia (Bruton agammaglob...

Epstein-Barr virus (EBV), implicated in numerous human diseases, including lymphoid malignancies, persistently infects peripheral B cells and transforms them into lymphoblastoid cell lines. Here we found that EBV equally infected B cells from patients with X-linked hyper IgM syndrome and those from healthy donors; however, it hardly transformed X-linked hyper IgM syndrome B cells, because of th...

We established a transformed B cell line expressing both IgM and IgG on the cell surface from a patient with hyper IgM immunodeficiency using Epstein-Barr viruses. DNA and RNA of the cells were analyzed. DNA rearrangements of Ig JH gene loci were observed on both chromosomes. Cloning and DNA sequence analyses showed that one has a VHDHJH structure while the other has a DHJH structure. Southern ...

X-linked hyper-IgM Syndrome (XHIGM) is caused by a mutation of CD40 ligand (CD40L), which is normally expressed on activated CD4+ T cells and is responsible for immunoglobulin class switching. A 7-year-old boy with recurrent sino-pulmonary infections since the age of 3 months had normal CD3+, CD4+, CD8+T lymphocytes, and CD19+B lymphocytes and NK cells, but significantly elevated IgM and extrem...

Junctions at class switch recombination sites in the genome are characterized by a unique sequence feature. Nucleotide substitutions and small deletions are common on either of the two sides of the switch junction, but not on both together. We have previously reported an extrachromosomal substrate assay system for analyzing the recombination of class switch sequences. Here we have sequenced nin...