Analysis of in vitro polyclonal B cell differentiation responses to bacterial peptidoglycan and pokeweed mitogen in rheumatoid arthritis.

To gain insight into possible determinants of in vivo polyclonal B cell activation seen in rheumatoid arthritis (RA), we enumerated immunoglobulin secreting cells appearing in cultures of peripheral blood mononuclear cells that were stimulated with pokeweed mitogen (PWM) or a newly described polyclonal B cell activator, bacterial peptidoglycan. Peptidoglycan, the major constituent of the cell wall of gram positive bacteria, has properties which warrant its consideration in the pathogenesis of RA; including the ability to induce rheumatoid factor production as well as a RA like syndrome in experimental animals. RA patients as a group had similar immunoglobulin secreting cell responses in PWM stimulated cultures compared to arthritis controls and showed moderately depressed responses compared to healthy volunteers. However, their in vitro responses to peptidoglycan were markedly depressed when compared to those of both control groups. Of note, severely reduced peptidoglycan-induced responses were seen in 26 of 55 rheumatoid patients who demonstrated intact PWM-induced responses. These impaired responses to peptidoglycan were not due to (1) aberrant kinetic response; (2) shift in the dose-response pattern; (3) decreased cell survival in culture or (4) the inability of peptidoglycan to activate RA cells. Cell fractionation studies indicated that peptidoglycan reactive B cells were present in the blood of some patients but their reactivity was abrogated by suppressor T cells. These studies provide evidence of aberrant in vitro polyclonal B cell activation in patients with RA and provide a basis for further investigation of peptidoglycan as an immunopathogenetic agent in this disease.