Multiple myeloma involves the unregulated proliferation of an antibody-producing plasma cell (myeloma cell) independently of antigen stimulation or T-cell help

Question

Myeloma cells populate multiple sites in the bone marrow, where they produce immense quantities of monoclonal immunoglobulin as well as suppressing normal marrow function. Myeloma cells also synthesize and secrete excessive amounts of free light chains (known as Bence-Jones protein), which, because of their low molecular weight (~25 kDa) are excreted as free light chains in the urine.
In a given patient the free light chains are both monoclonal and all are of either the ? or the ? type.
A. Explain both of these observations.
B. Why do you think patients with multiple myeloma are more susceptible than normal to pyogenic infections, such as pneumonia caused by Streptococcus pneumoniae or Haemophilus influenzae?

Answer 1

A. In a normal response to infection, a diverse array of plasma cells will produce different light chains against many different antigens. In multiple myeloma, the tumor originates from a single plasma cell expressing heavy and light chains with specificity for a single antigen (clonotypic immunoglobulin). Because B cells express only κ or λ light chains, the tumor will also express only κ or λ, but not both. Therefore, Bence-Jones protein for a given patient will be of one type or another, but not both.
B. Although patients will have elevated immunoglobulin levels (usually IgG or IgA), most of the immunoglobulin will be produced by the myeloma cells and will be monospecific. Hence, normal concentrations of polyclonal immunoglobulin will be severely compromised. Pyogenic infections caused by encapsulated bacteria are cleared by humoral immune responses that use antibody-mediated complement activation and antibody-enhanced phagocytosis. An insufficiency of pathogen-specific polyclonal immunoglobulins puts these patients at greater risk of these infections.