Abstract: The present invention relates to an lnterleukin-21 (IL-21) variant which is capable of increasing the secretion of IgG and/or IgA antibodies in B cells and/or is capable of binding the IL-2 receptor complex and/or the IL-4 receptor complex, comprising stretches of amino acids of lnterleukin-4 (IL-4) or lnterleukin-2 (IL-2) in substitution of amino acids of IL-21. The present invention also relates to a pharmaceutical composition comprising IL-21 and/or an IL-21 variant and at least one compound selected from IgA inducing protein (IGIP), Syntenin-1, Galectin-1 and Galectin-3. The present invention further relates to a pharmaceutical composition for the treatment of a primary humoral immunodeficiency disease comprising IL-21 and/or an IL-21 variant and IL-4 and/or IL-2 and/or IGIP and/or Syntenin-1 and/or Galectin-1 and/or Galectin-3.