Identification of germinal centres in the lymph node of a patient with hyperimmunoglobulin M syndrome associated with congenital rubella

J Clin Immunol. 2014 Oct;34(7):796-803. doi: 10.1007/s10875-014-0084-6. Epub 2014 Aug 12.

Abstract

Background: The hyper immunoglobulin M syndrome (HIM) associated with congenital rubella infection (rHIM) is an extremely rare disorder, where patients have elevated serum IgM in association with reduced IgG and IgA. We have previously shown that in contrast to X-linked HIM (XHIM), a patient with well-characterised rHIM is able to express functional CD40 ligand, undergo immunoglobulin isotype switching and to generate memory B cells. Here we describe the ultrastructural features of an excised lymph node from this patient.

Methods: An inguinal lymph node was surgically removed and examined histologically as well as by immunohistochemistry. It was then stained with multiple fluorescent dyes to visualize the cellular interactions within the node. Flow cytometry was undertaken on a cellular suspension from the node.

Findings: Our patient has normal lymph node architecture by light microscopy. Immunohistochemistry studies showed the presence of scattered germinal centres. Polychromatic immunofluorescence staining showed disruption of the architecture with mostly abnormal germinal centres. A small number of relatively intact germinal centres were identified. Both IgM and IgG bearing cells were identified in germinal centres.

Interpretation: In contrast to XHIM where germinal centres are absent, the presence of small numbers of relatively normal germinal centres explain our previous identification of isotype switched memory B cells in rHIM.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology*
  • CD40 Antigens / metabolism
  • Germinal Center / ultrastructure*
  • Humans
  • Hypergammaglobulinemia / complications
  • Hypergammaglobulinemia / immunology*
  • Immunoglobulin Class Switching / genetics
  • Immunoglobulin G / metabolism
  • Immunoglobulin M / metabolism
  • Immunoglobulins, Intravenous / administration & dosage
  • Immunologic Memory / genetics
  • Lymph Nodes / ultrastructure*
  • Male
  • Middle Aged
  • Rubella Syndrome, Congenital / complications
  • Rubella Syndrome, Congenital / immunology*

Substances

  • CD40 Antigens
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunoglobulins, Intravenous