REGULATION OF CELL MORPHOLOGY IN B-LYMPHOCYTES BY IL-4 - EVIDENCE FORINDUCED CYTOSKELETAL CHANGES

Lymphocyte activation is often accompanied by changes in cell morpholo gy, for example, in cell adhesion or motility, IL-4 is a cytokine exer ting many effects on B lymphocytes, In this study, we show that stimul ation with LPS in combination with IL-4, hut not LPS or IL-4 alone, re sults in a pronounced dendritic morphology of B cells. Using a culture system in which Abs directed to B cell surface markers are immobilize d on the tissue culture plastic, we find that cell spreading can be me diated by a variety of Abs, including anti-CD44, -CD23, -LFA-1, -VLA-4 , -ICAM-1, and -Ig, B cells stimulated with anti-Ig Abs plus IL-4, or anti-CD40 Abs in the presence or absence of IL-4, are also induced to spread, while IL-2, IL-5, or IL-10 in combination with LPS or alone fa il to induce this, Spreading correlates with induction of tight cell a ggregation. It is sensitive to cytochalasin B, indicating a requiremen t for intact actin cytoskeleton. CD44 is selectively detected in the d etergent-insoluble fraction of cell lysates prepared from LPS plus IL- 4-stimulated B cell cultures after Ab cross-linking of CD44, suggestin g a membrane protein-cytoskeleton interaction. Interestingly, electron microscopy studies reveal induction of microvilli-like structures on LPS plus IL-4-stimulated blasts, suggesting that IL-4 can influence ce ll morphology on an ultra-structural level. In summary, our data show that stimulation with LPS plus IL-4 or ligation of CD40 is capable of inducing dramatic morphologic changes in murine B cells, which correla tes with in vitro induction of strong cell adhesion.