Human B cells express IL-5 receptor messenger ribonucleic acid and respond to IL-5 with enhanced IgM production after mitogenic stimulation with Moraxella catarrhalis.
The potential for IL-5 to regulate human B cells is controversial despite its well established role as a regulatory factor for murine B cells. We hypothesized that the mechanism by which human B cells were stimulated would, as with murine B cells, determine their potential to respond to IL-5. Since Staphylococcus aureus Cowan strain I (SAC) and Moraxella catarrhalis (MCat) stimulate human B cells by distinct interactions with cell-surface Ig, we compared their potential to induce an IL-5-responsive state by human B cells purified to homogeneity. Neither SAC alone nor SAC plus IL-5 stimulated Ig production, although microgram quantities of IgM were produced with SAC plus IL-2. In contrast, MCat induced microgram quantities of IgM by B cells in the absence of exogenous cytokines, and IL-5 significantly increased IgM production over twofold in the majority of donors. Synergism of IL-5 and IL-2 was detected using suboptimal concentrations of IL-2 with MCat-, but not SAC-, stimulated B cells. Donor B cells unresponsive to IL-5 when stimulated with MCat, became IL-5 responsive in the presence of IL-2. Since message for the IL-5R alpha, IL-5R beta, and soluble IL-5R alpha chains was detected in freshly isolated B cells, we further investigated whether IL-5 responsiveness to MCat, but not SAC, was due to their differential regulation of IL-5R mRNA. Surprisingly, stimulation by either MCat or SAC, without or with IL-2, increased both IL-5R alpha and IL-5R beta mRNA and decreased soluble IL-5R alpha mRNA. These studies demonstrate that, as with murine B cells, human B cells express message for IL-5R but can respond to IL-5 only if appropriately stimulated to undergo terminal differentiation.
Huston
M M
MM
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, TX 77030, USA.
Moore
J P
JP
Mettes
H J
HJ
Tavana
G
G
Huston
D P
DP
D000942:Antigens, Bacterial / Q000276:immunology; D000955:Antigens, T-Independent; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D007075:Immunoglobulin M / Q000096:biosynthesis; D007376:Interleukin-2 / Q000502:physiology; D015848:Interleukin-5 / Q000502:physiology; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D001936:Moraxella catarrhalis / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics*; D053649:Receptors, Interleukin-5; D013211:Staphylococcus aureus / Q000276:immunology
D000942:Antigens, Bacterial; D000955:Antigens, T-Independent; D017931:DNA Primers; D007075:Immunoglobulin M; D007376:Interleukin-2; D015848:Interleukin-5; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053649:Receptors, Interleukin-5