J Korean Pediatr Soc.  2003 Feb;46(2):128-136.

Characterization of B Cells of Lymph Nodes and Peripheral Blood in a Patient with Hyper IgM Syndrome

• Kim DS
• Shin KM
• Yang WI
• Shin JS
• Song CH

Abstract

PURPOSE
Hyper IgM syndrome(HIGM) is characterized by severe recurrent bacterial infections with decreased serum levels of IgG, IgA, and IgE but elevated IgM levels. Recently, it has been classified into three groups; HIGM1, HIGM2 and a rare form of HIGM. HIGM1 is a X-linked form of HIGM and has now been identified as a T-cell deficiency in which mutations occur in the gene that encodes the CD40 ligand molecule. HIGM2 is an autosomal recessive form of HIGM. Molecular studies have shown that the mutation of HIGM2 is in the gene that encodes activation-induced cytidine deaminase(AID). Recently, another rare form of X-linked HIGM syndrome associated with hypohydrotic ectodermal dysplasia has been identified. We encountered a patient with a varient form of HIGM2. To clarify the cause of this form of HIGM, we evaluated the peripheral B cells of this patient.
METHODS
The lymphocytes of the patient were prepared from peripheral blood. B cells were immortalized with the infection of EBV. Cell cycle analysis was done with the immortalized B cells of the patient. Peripheral mononuclear cells were stained with monoclonal anti-CD40L antibody. Total RNA was extracted from the peripheral mononuclear cells. After RT-PCR, direct sequencing for CD40L gene and HuAID gene were done. Immunostainings of a lymph node for CD3, CD23, CD40, Fas-L, bcl-2, BAX were done.
RESULTS
The peripheral B cells of this patient showed normal expression of CD40L molecule and normal sequencing of CD40L gene, and also normal sequencing of AID gene. Interestingly, the peripheral B cells of this patient showed a decreased population of G2/mitosis phase in cell cycles which recovered to normal with the stimulation of IL-4.
CONCLUSION
We suspect that the cause of increased serum IgM in this patient may be from a decrease of G2/mitosis phase of the peripheral B cells, which may be from the decreased production or secretion of IL-4. Therefore, this may be a new form of HIGM.

Keyword

Hyper IgM Syndrome; CD40L; AID; Cell Cycle

MeSH Terms

B-Lymphocytes*
Bacterial Infections
CD40 Ligand
Cell Cycle
Cytidine
Ectodermal Dysplasia
Herpesvirus 4, Human
Humans
Hyper-IgM Immunodeficiency Syndrome*
Hyper-IgM Immunodeficiency Syndrome, Type 1
Immunoglobulin A
Immunoglobulin E
Immunoglobulin G
Immunoglobulin M
Interleukin-4
Lymph Nodes*
Lymphocytes
RNA
T-Lymphocytes
CD40 Ligand
Cytidine
Immunoglobulin A
Immunoglobulin E
Immunoglobulin G
Immunoglobulin M
Interleukin-4
RNA