SEQUENCE-ANALYSIS OF HUMAN IGV(H) GENES INDICATES THAT ILEAL LAMINA PROPRIA PLASMA-CELLS ARE DERIVED FROM PEYERS-PATCHES

The origin of human ileal lamina propria (LP) plasma cells has been in vestigated using a technique based on microdissection of cells from im munohistochemically stained tissue sections. We have sequenced rearran ged IgV(H)4.21, IgV(H)5 family and IgV(H)6 genes from Peyer's patch ge rminal center (GC) cells and plasma cells from the ileal LP. Clonally related cells were identified by comparison of their complementarity d etermining region (CDR) 3 sequences and patterns of somatic mutation. We observed Ig genes from B cells in the GC of Peyer's patches which w ere related to Ig genes from plasma cells in the ileal LP, demonstrati ng that clonally related cells span these sites. In addition, groups o f clonally related, but diversified plasma cells were common in the la mina propria. All Ig genes isolated from LP plasma cells were heavily mutated. The distribution of mutations in the CDR of the Ig heavy chai n variable region (V-H) genes which were considered to be the expresse d alleles in LP plasma cells was consistent with an affinity-matured r esponse. These observations provide compelling evidence for the origin of human ileal plasma cells from the Peyer's patches.