Induction of human B cell differentiation by Fc region activators. I. Identification of an active tetrapeptide.
Addition of pFc' fragments, composed of residues 334 to 446 in the Fc region of human IgG1, to cultures of human peripheral blood mononuclear cells resulted in the induction of Ig-secreting cells (ISC). Intact IgG1 and F(ab')2 fragments were inactive. The synthetic peptide p23, representing residues 335 to 357, retained the ISC-inducing property of pFc' fragments. The ISC response to p23 exhibited the isotype pattern IgMSC greater than IgGSC greater than or equal to IgASC. Results from cell depletion experiments revealed that the B cell response to p23 was T cell dependent but relatively monocyte independent. Cell proliferation was not increased in p23-stimulated PBMC cultures. Overlapping synthetic peptides based on the sequence of p23 were used to localize the active site in this molecule. These studies revealed that LPPSR (residues 351 to 355) was the sequence responsible for the ISC-inducing property of p23; however, expression of activity by this pentapeptide sequence could be dampened by N-flanking sequences. Finally, residue-deleted analogs of LPPSR were used to determine that LPPS was the minimum sequence retaining activity. Collectively, these data suggest that the fragmentation of IgG results in the expression of a tetrapeptide sequence with lymphocyte-stimulating properties.
Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
M V
MV
Hobbs
R A
RA
Houghten
J A
JA
Janda
W O
WO
Weigle
E L
EL
Morgan
D000595:Amino Acid Sequence; D000921:Antibody-Producing Cells / Q000502:physiology; D001402:B-Lymphocytes / Q000502:physiology*; D001665:Binding Sites; D002454:Cell Differentiation / Q000187:drug effects; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000502:physiology*; D015847:Interleukin-4; D007378:Interleukins / Q000502:physiology*; D008297:Male; D010455:Peptides / Q000138:chemical synthesis / Q000502:physiology*
D007141:Immunoglobulin Fc Fragments; D007378:Interleukins; D010455:Peptides; D015847:Interleukin-4