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Updated: Aug 10, 2026
Passive Administration of Monoclonal Antibodies Against H. capsulatum and Others Fungal Pathogens
Published on: February 15, 2011
The mouse antibody response to infection with Cryptococcus neoformans: VH and VL usage in polysaccharide binding
1Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461.
Abstract:
Cryptococcus neoformans is a ubiquitous fungus that can cause serious infections in humans. The fungus has a polysaccharide (C. neoformans capsular polysaccharide; CNPS) capsule that contributes to its pathogenicity and can elicit an antibody response. Nevertheless, only 4 of 60 BALB/c mice chronically infected with C. neoformans had a detectable increase in serum anti-CNPS. The sera of three responder mice contained both IgM and IgG anti-CNPS antibody, and the titers of lambda and kappa anti-CNPS antibody were approximately equal. Eight IgM and one IgG3 monoclonal antibodies (mAbs) were generated from the spleen of one responder mouse, and one IgA was generated from the spleen of another mouse. Seven of the IgMs, the IgG3, and the IgA mAb had lambda light chains and were specific for serotype D CNPS. Molecular analysis confirmed that this was a highly restricted antibody response. All of the D-specific antibodies used VH441, JH3, and either V lambda 2/J lambda 2 or V lambda 1/J lambda 1, and all had the same heavy chain CDR3 amino acid sequence, even though there were differences in the nucleotide sequence of the N/D segment. One IgM mAb reacted with both serotype A and D CNPS, and this mAb used different VH and JH genetic elements and had kappa light chains. All the anti-CNPS mAbs used J proximal VH gene elements that have previously been shown to bind dextran and other polysaccharides. Sequence and Southern blot analysis indicate that the serotype-D CNPS-specific mAbs arose from only a few precursor B cells.
Insights
A study on Cryptococcus neoformans infections found a limited antibody response to its capsule. Monoclonal antibodies revealed a restricted B cell response, primarily targeting serotype D capsular polysaccharide.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Cryptococcus neoformans causes serious human infections.
- Its capsular polysaccharide (CNPS) is key to pathogenicity and can trigger antibody responses.
- However, a detectable anti-CNPS antibody response is rare in infected mice.
Purpose of the Study:
- To investigate the nature and restriction of the antibody response to C. neoformans capsular polysaccharide (CNPS).
- To characterize the monoclonal antibodies (mAbs) generated against CNPS.
- To understand the B cell precursor origins of the anti-CNPS antibody response.
Main Methods:
- Chronic infection model in BALB/c mice.
- Generation and characterization of monoclonal antibodies (mAbs) from responder mice.
- Molecular analysis of antibody gene usage (VH, JH, V lambda, J lambda) and CDR3 sequences.
- Serotype specificity testing (A and D).
- Southern blot analysis.
Main Results:
- A highly restricted antibody response was observed in mice infected with C. neoformans.
- Most generated mAbs were lambda light chain-positive and specific for serotype D CNPS.
- These D-specific mAbs shared common VH, JH gene elements, and heavy chain CDR3 sequences.
- Sequence and Southern blot analysis suggest a limited number of B cell precursors for serotype-D specific mAbs.
- One cross-reactive IgM mAb (serotypes A and D) utilized different VH/JH elements and kappa light chains.
Conclusions:
- The antibody response to C. neoformans capsular polysaccharide is highly restricted, particularly for serotype D.
- A few B cell precursors, utilizing specific VH gene elements, likely generate the dominant anti-CNPS antibody repertoire.
- This restricted response may have implications for vaccine development and understanding host immunity to Cryptococcus.
