Neutral glycosphingolipids of the globo-series characterize activation stages corresponding to germinal center B cells

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Abstract
The neutral glycosphlngolipid (GSL) globotriaosylceramlde (Gb3) of the globo-serles was recently defined as the CD77 antigen. This B cell-associated antigen is characterized by its specific expression on germinal center B cells. In order to study the potential relation of the CD77 antigen and other GSLs to B cell activation we have performed a comprehensive analysls of the synthesis and expression of neutral GSL in tonsillar B lymphocytes. Monoglycosylceramide (GL1) and lactosylceramide (LacCer) comprised the largest portion of GSL In tonsillar B lymphocytes as detected by HPLC analysis. GSLs of the globo-series Gb3 and globotetraosylceramlde (Gb4), were found in smaller amounts. Since other GSLs, like gangliotrlaosylcerarnlde(Gg4) and gangliotetraosylceramide (Gg4), could only be detected using highly sensitive antibody reactions, we assume that these GSLs occur In B cells only In minor amounts. When tonsillar B cells were density fractionated on Percoll, the llght density cells, which correspond to activated cells, contained and expressed more of both globo-GSLs than cells In the higher density traction. When the dense fraction of tonsillar B cells was activated in vitro, by antl-μ/BCGF, synthesls of GL1, LacCer, Gb3, and Gb4, was biphasic, with rnaxlma at 12 and 84 h. Surface expression of the CD77 antigen on the denser cells was strongly induced by anti-cJBCGF during the first 24 h of cultivation followed by a rapid decline thereafter, mimicklng synthesls. PMA treatment of this cell fraction caused an even stronger expression of the CD77 antigen, whlch lasted over 48 h of cultivation. Thus, during B cell activation the kinetics and intensity of GSL synthesis and expression may vary depending upon the type of stimulus. In situ, only tonsillar B cells of the germinal center expressed the CD77 antigen. Together, these results point to an involvement of globo-series GSLs, In particular the CD77 antigen, in B cell activation.