Casadevall A, Scharff M D
Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York 10461.
J Exp Med. 1991 Jul 1;174(1):151-60. doi: 10.1084/jem.174.1.151.
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.
新型隐球菌是一种广泛存在的真菌，可导致人类严重感染。该真菌具有多糖（新型隐球菌荚膜多糖；CNPS）荚膜，这有助于其致病性，并能引发抗体反应。然而，在60只长期感染新型隐球菌的BALB/c小鼠中，只有4只血清中可检测到抗CNPS的增加。三只产生反应的小鼠血清中同时含有IgM和IgG抗CNPS抗体，λ和κ抗CNPS抗体的效价大致相等。从一只产生反应的小鼠脾脏中产生了8种IgM和1种IgG3单克隆抗体（mAb），从另一只小鼠脾脏中产生了1种IgA。其中7种IgM、IgG3和IgA mAb具有λ轻链，对D血清型CNPS具有特异性。分子分析证实这是一种高度受限的抗体反应。所有D特异性抗体均使用VH441、JH3以及Vλ2/Jλ2或Vλ1/Jλ1，并且即使N/D区段的核苷酸序列存在差异，所有抗体的重链CDR3氨基酸序列相同。一种IgM mAb可与A血清型和D血清型CNPS发生反应，该mAb使用不同的VH和JH基因元件，并具有κ轻链。所有抗CNPS mAb均使用靠近J的VH基因元件，这些元件先前已被证明可结合葡聚糖和其他多糖。序列分析和Southern印迹分析表明，D血清型CNPS特异性mAb仅来自少数前体B细胞。
