TAF(II)105 is a TFIID-associated factor highly expressed in B lymphocytes. This subunit is found in a small portion of TFIID complexes and is homologous to human TAF(II)130 and Drosophila TAF(II)110. In the present study we show that TAF(II)105 is involved in transcription activation directed by the B cell-specific octamer element found in many B cell-specific genes. B cells overexpressing TAF(II)105 display higher octamer-dependent transcription, whereas expression of a C-terminal truncated form of TAF(II)105 inhibits octamer transcription in a dominant negative manner. In addition, antibodies directed against TAF(II)105 specifically inhibit octamer-dependent transcription. Reporter gene analysis revealed that TAF(II)105 elevates octamer transcription in the presence of OCA-B, a cofactor subunit of Oct1 and Oct2 proteins. In vitro binding assays and functional studies established that the effect of TAF(II)105 on octamer activity involves interaction of TAF(II)105 with octamer-binding complexes via the C-terminal activation domain of OCA-B. These findings link TAF(II)105 coactivator function to B cell-specific transcription.